Structure of 6018-89-9
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CAS No. : | 6018-89-9 |
Formula : | C4H14NiO8 |
M.W : | 248.84 |
SMILES Code : | CC([O-])=O.CC([O-])=O.[H]O[H].[H]O[H].[H]O[H].[H]O[H].[Ni+2] |
MDL No. : | MFCD00066973 |
InChI Key : | OINIXPNQKAZCRL-UHFFFAOYSA-L |
Pubchem ID : | 62601 |
GHS Pictogram: |
![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302+H332-H317-H334-H341-H350-H360-H372-H410 |
Precautionary Statements: | P201-P260-P273-P280-P304+P340+P312-P308+P313-P391 |
Class: | 9 |
UN#: | 3077 |
Packing Group: | Ⅲ |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 8.0 |
Num. H-bond donors | 4.0 |
Molar Refractivity | 35.31 |
TPSA ? Topological Polar Surface Area: Calculated from |
117.18 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-2.32 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-2.74 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-3.77 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.48 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-1.86 |
Log S (ESOL):? ESOL: Topological method implemented from |
0.08 |
Solubility | 298.0 mg/ml ; 1.2 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.4 |
Solubility | 619.0 mg/ml ; 2.49 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.53 |
Solubility | 851.0 mg/ml ; 3.42 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-9.47 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.39 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate; In ethanol; at 60 - 70℃; | General procedure: To a flask containing ethanol solution of reagent 3 (1 equiv.), Ni(OAc)2·4H2O (4 equiv.), racemic amino acid (2.0 equiv.), was added K2CO3 (15 equiv.), and the reaction mixture was stirred at 60-70 C. The progress of the reaction was monitored by TLC and upon completion (consumption of the reagent 3), the reaction mixture was poured into ice water. The target product was extracted several times with CH2Cl2. The combined organic layer was dried over anhydrous MgSO4 and evaporated under vacuum. After evaporation of the solvents and silica-gel column chromatography, the target complexes 5a-c and 6a,b were obtained in diastereomerically pure form. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In methanol; for 3h;Reflux; | To a stirring solution of sapH2 ligand (0.106 g, 0.5 mmol) inmethanol (10 mL), an equimolar solution of Ni(OAc)24H2O(0.124 g, 0.5 mmol) in 10 mL methanol was added drop-wise fromthe dropping funnel. The resulting solution was stirred and heated.Then 0.034 g (0.5 mmol) methanolic solution of the imidazole wasadded to reaction mixture. The reaction mixture was refluxed for3 h. The single crystals suitable for X-ray data collection wereobtained by slow evaporation of the methanol solution after days.The crystals were filtered off, washed with a small amount of coldmethanol and dried under vacuum. Scheme 1 shows the schematicrepresentation of the synthetic procedure for the preparation ofthe complexes. Yield: 85%. Red color crystals. Mol. Wt.: 337.98Anal. Calc. for C16H13N3NiO2: C, 56.87; H, 3.87; N, 12.43. Found:C, 56.57; H, 3.69; N, 12.35%. FT-IR: mmax cm1 (KBr): 1606 (CN),1273 (C-O), 3147 (N-H), 3053 (C-H Ar), 1483, 1527 (CC Ar),2852 (C-H). UV-Vis: kmax (nm) (e, M1 cm1) (CH3CN): 246(41900), 269 (21800), 297 (8400), 418 (19500), 439 (16300), 527(820), 1H NMR (CDCl3, 400 MHz): 6.55 (m, 1H, Ar), 6.69 (m, 1H,Ar) 6.75 (dd, 1H, Ar), 6.94 (dbr, 1H, Ar), 7.01 (m, 2H, Ar), 7.22 (m,2H, Ar), 7.42 (d-d, 1H, Ar), 7.59 (dd, 1H, Ar), 7.87 (s, 1H, Ar), 8.15(s, 1H, CHN), 9.9 (s, 1H, NH). |
75% | In methanol; acetonitrile; for 2h;Reflux; | General procedure: We added a solution of nickel(II) acetate tetrahydrate (0.497g; 0.002mol) in MeOH (30mL) and solid PPh3 (0.524g; 0.002mol) to a solution of Schiff base H2L (0.426g; 0.002mol) in MeCN (30mL). The resulting solution was refluxed for 2h and then left to evaporate slowly at ambient temperature. Well shaped red-brown crystals of complex 5a suitable for single crystal X-ray structure analysis were collected after few days by filtration, washed with methanol and finally dried at ambient temperature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | In ethanol; for 3h;Reflux; | This complex was prepared by the same method as for complex(1), except that 0.041 g (0.5 mmol) of the 1-Me-imidazole was usedinstead of imidazole and ethanol was used as solvent. Red crystalssuitable for X-ray crystallography were produced by slow evaporationof reaction solution at room temperature. The crystals were filtered off, washed with a small amount of cold ethanol and driedunder vacuum. Yield: 83%. Red color crystals. Mol. Wt.: 352.01Anal. Calc. for C17H15N3NiO2: C, 56.01; H, 4.29; N, 11.93. Found:C, 55.50; H, 4.21; N, 11.89%. FT-IR: mmax cm1 (KBr): 1603(CN),1273 (C-O), 3111 (C-H Ar) 1527,1481 (CC Ar), UV-Vis: kmax(nm) (e, M1 cm1) (CH3CN): 246 (41700), 267 (21800), 294(8300), 420 (19500), 439 (16100), 535 (845), 1H NMR (CDCl3,400 MHz): 3.75 (s, 3H), 6.55 (m, 1H, Ar), 6.68 (m, 1H, Ar), 6.75(dd, 1H, Ar) 6.85 (t, 1H, Ar), 6.95 (dbr, 1H, Ar), 7 (m, 1H, Ar) 7.13(t, 1H, Ar), 7.22 (m, 1H, Ar), 7.41 (dd, 1H, Ar), 7.58 (dd, 1H, Ar),7.7 (s, 1H, Ar), 8.15 (s, 1H, CHN). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | In methanol; for 3h;Reflux; | This complex was prepared by the same method as for complex(1), except that 1 mL of the morpholine was used instead of imidazole.The resulting precipitate after 3 h reflux, was filtered off,washed with 10 mL of methanol and air dried. Recrystallizationfrom chloroform and ethanol yielded single crystals of complexsuitable for X-ray crystallography. The crystals were filtered off,washed with a small amount of cold ethanol and dried under vacuum.Yield: 86%. Red color crystals. Mol. Wt.: 356.02 Anal. Calc. forC17H18N2NiO3: C, 57.35; H, 4.81; N, 7.86. Found: C, 56.14; H, 4.56;N, 7.80%. FT-IR: mmax cm1 (KBr): 1603(CN), 1273 (C-O) 1483, 527(CC) 3275 (N-H) 2848, 2954 (C-H mrpln). UV-Vis: kmax (nm) (e,M1 cm1) (CH3CN): 243 (43800), 266 (21600), 295 (7100), 416(19900), 437 (16600), 520 (800), 1H NMR (CDCl3, 400 MHz): 2.09(t, H, NH) 3.23 (m, 2H, CH2), 3.41 (dbr, 2H, CH2), 3.61 (t-d, 2H,CH2), 3.95 (d-d, 2H, CH2), 6.55 (m, 1H, Ar), 6.69 (m, 2H, Ar), 6.91(dbr, 1H, Ar), 7.01 (m, 1H, Ar), 7.23(m, 1H Ar), 7.38 (d-d, 1H, Ar),7.52 (d-d, 1H, Ar), 8.15 (s, 1H CHN). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2%; 21%; 12%; 15% | at 210℃; for 1h; | Nickel complexes 3?6. A mixture of 1.00 g (3.2 mmol) of nitrile 1, 0.64 g (3.2 mmol) of nitrile 2, and 0.50 g (2.0 mmol) of nickel(II) acetate tetrahydrate was stirred during 1 h at 210 °C. After cooling the reaction mixture, it was dissolved in 50 mL of dichloromethane and filtered through a 5 cm layer of type II alumina. The solvent was distilled off, and the residue was purified by column chromatography on Kieselgel 60 silica gel (Merck). First, complexes 3 and 4 were isolated using dichloromethane as eluent, and then complexes 5 and 6 were isolated using a 95 : 5 (v/v) mixture of dichloromethane and ethanol as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | In methanol; acetonitrile; for 2h;Reflux; | We added a solution of nickel(II) acetate tetrahydrate (0.497g; 0.002mol) in MeOH (30mL) and solid PPh3 (0.524g; 0.002mol) to a solution of Schiff base H2L (0.426g; 0.002mol) in MeCN (30mL). The resulting solution was refluxed for 2h and then left to evaporate slowly at ambient temperature. Well shaped red-brown crystals of complex 5a suitable for single crystal X-ray structure analysis were collected after few days by filtration, washed with methanol and finally dried at ambient temperature. Yield: 78%, 1H NMR (600MHz, C6D6): δ=8.04 (s, 1H), 7.93 (br s, 6H), 7.31 (d, 1H, J=8.2Hz), 7.11 (d, 1H, J=7.9Hz), 7.09-7.02 (m, 9H), 6.99 (dd, 1H, J=8.5, 6.9Hz), 6.96 (dd, 1H, J=8.2, 7.1Hz), 6.88 (d, 1H, J=8.2Hz), 6.62 (d, 1H, J=8.5Hz), 6.57 (dd, 1H, J=7.9, 6.9Hz), 6.55 (1H, dd, J=8.2, 7.1Hz); 13C NMR (151MHz, CDCl3): δ=167.0, 163.6, 148.4, 139.7, 135.0 (m, 6×C), 133.2, 132.5, 130.5 (3×C), 129.9 (only seen in HMBC, 3×C), 128.8, 128.6 (6×C), 122.4, 121.0, 118.6, 115.7, 114.7 (2×C); Elemental Anal. Calc.: C, 69.96; H, 4.55; N, 2.63; Found: C, 69.72; H, 4.72; N, 2.85%. IR (ATR) cm-1: ν(C=N) 1606 s, ν(C-O) 1311 m, ν(Ni-P) 1098 s, ν(Ni-O) 527 s, ν(Ni-N) 454 s, UV-Vis (NUJOL) λmax cm-1: 23500, 21250. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | In methanol; acetonitrile; for 2h;Reflux; | General procedure: We added a solution of nickel(II) acetate tetrahydrate (0.497g; 0.002mol) in MeOH (30mL) and solid PPh3 (0.524g; 0.002mol) to a solution of Schiff base H2L (0.426g; 0.002mol) in MeCN (30mL). The resulting solution was refluxed for 2h and then left to evaporate slowly at ambient temperature. Well shaped red-brown crystals of complex 5a suitable for single crystal X-ray structure analysis were collected after few days by filtration, washed with methanol and finally dried at ambient temperature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | In methanol; acetonitrile; for 2h;Reflux; | General procedure: We added a solution of nickel(II) acetate tetrahydrate (0.497g; 0.002mol) in MeOH (30mL) and solid PPh3 (0.524g; 0.002mol) to a solution of Schiff base H2L (0.426g; 0.002mol) in MeCN (30mL). The resulting solution was refluxed for 2h and then left to evaporate slowly at ambient temperature. Well shaped red-brown crystals of complex 5a suitable for single crystal X-ray structure analysis were collected after few days by filtration, washed with methanol and finally dried at ambient temperature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In methanol; acetonitrile; for 2h;Reflux; | General procedure: We added a solution of nickel(II) acetate tetrahydrate (0.497g; 0.002mol) in MeOH (30mL) and solid PPh3 (0.524g; 0.002mol) to a solution of Schiff base H2L (0.426g; 0.002mol) in MeCN (30mL). The resulting solution was refluxed for 2h and then left to evaporate slowly at ambient temperature. Well shaped red-brown crystals of complex 5a suitable for single crystal X-ray structure analysis were collected after few days by filtration, washed with methanol and finally dried at ambient temperature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.5%; 12%; 18%; 14% | With urea; at 200℃; for 1h; | A mixture of 1.0 g (3 mmol) of nitrile 1, 0.6 g (3 mmol) of nitrile 2, 0.50 g (2.0 mmol) of nickel acetate tetrahydrate, and 1.0 g of urea was heated with stirring for 1 h at 200°C. The reaction mass was cooled, suspended in 50 ml of chloroform, and filtered through a layer of alumina of the II grade of activity 10 cm thick. From the filtrate the solvent was removed, the residue was dissolved in chloroform and subjected gel-permeation chromatography on a column filled with sorbent BIORAD® Bio-Beads SX-1 (eluent chloroform). The mixture was separated in four zones containing respectively complexes 3?6. After removal of the solvent individual complexes were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
for 2.0h;Heating; | General procedure: The nickel(II) complexes, chlorhexidinenickel(II) chloride dihydrate (complex 1), chlorhexidinenickel(II) bromide dihydrate (complex 2) and chlorhexidinenickel(II) acetate ethanolate(complex 3), were prepared by the following general method. <strong>[56-95-1]Chlorhexidine diacetate</strong>monohydrate, 0.6435 g (1 mmol), was dissolved in 30 mL ethanol, under slight heating. Therequired solid metal salt, i.e., NiCl2·6H2O (0.2377 g, 1.0 mmol for complex 1), NiBr2·(0.2185g, 1.0 mmol for complex 2) and Ni(CH3COO)2·4H2O (0.2486 g, 1.0 mmol for complex 3),was added slowly under stirring, keeping the temperature below 40 C. The color of thesolutions became orange after a few minutes. The precipitate began to form after 2 h of stirringwith heating. The mixture was left overnight and then the orange precipitate was filteredoff, washed with ethanol and dried under air. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | In water; for 504h; | General procedure: General procedure: An aqueous solution (3 mL) of the metalsalts (0.025 mmol) [1: Ni(OAc)2.4H2O; 2 and 3: CuBr2] was carefullylayered above a DMF solution (3 mL) of the ligand(0.05 mmol) [1 and 2: 4-PPT; 3: 3-PPT]. After about three weeks,diffraction quality single crystals resulted at the interface betweenthe aqueous and DMF layer.1 (wine red). Yield: 32% (based on 4-PPT). IR (KBr, cm-1): 1613(w), 1557 (s), 1407 (w), 1348 (s), 1170 (w),807 (w), 647 (w). C24-H26N8NiO2S2 Calc.: C, 49.58; H, 4.51; N, 19.28. Found: C, 49.37;H, 4.42; N, 19.55%. |