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Type | HazMat fee for 500 gram (Estimated) |
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Structure of 1208-52-2
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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Maria Hoppe ; Margit Gmeiner ; Petra Schmid ;
Abstract: Primary aromatic amines (PAAs) may be found in food contact materials and can potentially migrate from packaging material into the packed foodstuffs. Certain members of this substance class are of particular concern due to their toxicological properties. Legislators and authorities require a risk assessment regarding the transfer of PAAs into food. The evaluation of PAAs’ migration into food relies on migration or extraction tests using aqueous and acidic food simulants or solvents. However, PAAs exhibit stability issues in acidic media, which could lead to an underestimation of migration. Therefore, a systematic stability study was conducted for 28 PAAs in 3% acetic acid and water at different storage conditions. Standard solutions of 2 and 10 ng/ml of the amines in these media were prepared and stored under the following conditions: 2 h at 40 °C, 70 °C, and 100 °C, and 10 days at − 20 °C, 4 °C, 20 °C, 40° C, and 60 °C. The test solutions were analyzed using liquid chromatography coupled to mass spectrometry, and recovery was calculated against freshly prepared standard solutions. It was found that several PAAs undergo a loss of recovery under the investigated conditions; 7 of the substances were identified to be the most unstable: 3,3ʹ-dimethoxybenzidine, 3,3ʹ-dimethylbenzidine, 6-methoxy-m-toluidine, 4-methoxy-m-phenylendiamine, 2,6-toluenediamine, benzidine and 2,4-toluenediamine. It was concluded that both time and storage temperature play a pivotal role in the stability of PAAs. The experiments also demonstrated that PAAs exhibit greater stability in water than in 3% acetic acid.
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Keywords: Primary aromatic amines ; Food contact materials ; Migration and extraction testing ; PAA stability
Show More >
CAS No. : | 1208-52-2 |
Formula : | C13H14N2 |
M.W : | 198.26 |
SMILES Code : | NC1=CC=C(CC2=C(N)C=CC=C2)C=C1 |
MDL No. : | MFCD01670227 |
InChI Key : | UTNMPUFESIRPQP-UHFFFAOYSA-N |
Pubchem ID : | 14580 |
GHS Pictogram: |
![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H301+H311+H331-H317-H319-H341-H410 |
Precautionary Statements: | P261-P273-P280-P301+P310-P305+P351+P338 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅱ |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.08 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 64.7 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.04 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.73 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.46 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.69 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.42 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.29 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.9 |
Solubility | 0.248 mg/ml ; 0.00125 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.91 |
Solubility | 0.246 mg/ml ; 0.00124 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.61 |
Solubility | 0.00492 mg/ml ; 0.0000248 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
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 |
Yes |
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) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
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 |
-5.96 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 |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
1.0 alert |
Brenk? Structural Alert: implemented from |
1.0 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) |
1.48 |
* 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 |
---|---|---|
44.5% | Stage #1: at 25 - 80℃; Stage #2: at 45 - 140℃; for 2.5 - 2.83333 h; Stage #3: With sodium hydroxide In water at 100℃; |
Example 1 a) Preparation of the polyamine mixture: In a stirred vessel, 2600 g of aniline were intimately mixed at 25°C with 1000 g of formalin (30 wt.percent aqueous solution), with stirring until the mixture warmed up to 60°C. The stirrer was stopped and the upper, aqueous phase was separated off. 68 g of 30 wt.percent aqueous hydrochloric acid were then admixed, with renewed stirring and cooling. The temperature was kept at 45°C. After stirring for a further 15 min at this temperature, the cooling was replaced by heating and the mixture was heated uniformly to 140°C over 120 min under 5 bar pressure and then kept at this temperature for 15 min. The mixture was then cooled to 100°C, let down to normal pressure and neutralized by adding 54 g of 50 wt.percent aqueous sodium hydroxide solution, with stirring. After the stirrer had been stopped, the phases were left to settle and the lower, aqueous phase was siphoned off. Excess aniline with residual water was then distilled off, initially under normal pressure, and the aniline residues were removed by distilling the resulting polyamine mixture at 100 mbar and 250°C. This yielded 1900 g of a polyamine mixture having the following composition: 4,4'-MDA: 60.1 wt.percent2,4'-MDA: 6.0 wt.percent2,2'-MDA: 0.2 wt.percenthigher-molecular polyamines: 33.7 wt.percent; Example 2 a) Preparation of the polyamine mixture: In a stirred vessel, 1800 g of aniline were intimately mixed at 30°C with 1000 g of formalin (30 wt.percent aqueous solution), with stirring. The mixture was warmed up to 80°C. The stirrer was stopped and the upper, aqueous phase was separated off. 23 g of 30 wt.percent aqueous hydrochloric acid were then admixed, with renewed stirring and cooling. The temperature was kept at 45°C. After stirring for a further 15 min at this temperature, the cooling was replaced by heating and the mixture was heated uniformly to 140°C over 150 min under 5 bar pressure and then kept at this temperature for 20 min. The mixture was then cooled to 100°C, let down to normal pressure and neutralized by adding 18 g of 50 wt.percent aqueous sodium hydroxide solution, with stirring. After the stirrer had been stopped, the phases were left to settle and the lower, aqueous phase was siphoned off. Excess aniline with residual water was then distilled off, initially under normal pressure, and the aniline residues were removed by distilling the resulting polyamine mixture at 100 mbar and 250°C. This gave 1880 g of a polyamine mixture having the following composition: 4,4'-MDA: 44.5 wt.percent2,4'-MDA: 7.3 wt.percent2,2'-MDA: 0.5 wt.percenthigher-molecular polyamines: 47.7 wt.percent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66.75 %Chromat. | Stage #1: at 38 - 90℃; Stage #2: With sodium hydroxide In water |
Example 1:; Hydrochloric acid (a concentration percentage by weight is 30.8percent, this hydrochloric acid is a by-product from MDI apparatus) from storage tank 2 and aniline from storage tank 3 are fed into venturi mixer 5 by a pump 6 with a molar ratio of hydrochloric acid/anilin=0.36:1, for mixing and reacting with each other to produce aniline hydrochloride which is then pumped into circulation pipes and mixed with a circulation solution coming from a condensation stirred vessel 1 to obtain a mixed solution. The obtained mixed solution is introduced into a heat exchanger 7 to remove the reaction heat, and the mixed solution, which is cooled to 38°C and left the heat exchanger 7, is introduced into a feeding port of the high gravity rotating bed reactor 8 of rotating packed bed type. Formaldehyde solution (a concentration percentage by weight is 37 wtpercent) stream from storage tank 4 is fed through another feeding port of the high gravity rotating bed reactor 8, the ratio of formaldehyde to aniline is controlled at 0.40:1. The formaldehyde solution is mixed sufficiently with the previously mixed solution phase and conducted a pre-condensation reaction in the high gravity rotating bed reactor 8, the reaction temperature is controlled at 35°C, the reaction time is 0.5 sec, and the rotation speed of the rotor of high gravity rotating bed reactor is 1000rpm. Then the mixed reaction solution flows into the condensation reaction vessel 1 to proceed with the pre-condensation reaction, the temperature of reaction solution is controlled at 42°C, the stirring speed is about 110rpm, and the reaction residence time is about 20 min. Then the temperature of reaction solution is elevated to over 90°C to conduct a molecular rearrangement reaction, the residence time for molecular rearrangement reaction is about 2 hours. Finally a solution of diphenylmethylene diamine hydrochloride and polymethylene polyphenyl polyamines hydrochloride is obtained. 92 vol percent of the reaction mixture from the condensation reaction vessel 1 returns to the circulation pipes, as circulation solution, and flows to heat exchanger 7, the other 8 vol percent of the reaction mixture is discharged and neutralized with a sodium hydroxide solution at a concentration of 42 wtpercent. The salt water phase is separated from the polyamine organic phase, and the polyamines are washed with water and purified to finally obtain a mixture of diphenylmethylene diamine and polymethylene polyphenyl polyamines. The composition of products is listed in table 2. |
A831836 [78525-34-5]
4,4',4'',4'''-(Ethene-1,1,2,2-tetrayl)tetraaniline
Similarity: 0.93
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