Structure of 50594-82-6
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CAS No. : | 50594-82-6 |
Formula : | C7H2Cl3F3 |
M.W : | 249.45 |
SMILES Code : | FC(C1=CC(Cl)=C(Cl)C(Cl)=C1)(F)F |
MDL No. : | MFCD00035985 |
Boiling Point : | No data available |
InChI Key : | FBKFIAIRSQOXJR-UHFFFAOYSA-N |
Pubchem ID : | 2733399 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 46.47 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.41 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.69 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.82 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
5.07 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
4.8 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.56 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.62 |
Solubility | 0.00603 mg/ml ; 0.0000242 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.42 |
Solubility | 0.00953 mg/ml ; 0.0000382 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.14 |
Solubility | 0.00182 mg/ml ; 0.00000729 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-4.49 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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 |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.61 |
* 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 |
---|---|---|
75% | With potassium fluoride; nitrobenzene In sulfolane at 200 - 220℃; for 17 h; | Example 3; Preparation method of 3,4,5-trifluorobenzotrifluoride; 860 g of dry sulpholane and 524 g of dry KF were initially charged with exclusion of moisture in an autoclave, and 500 g of 3,4,5-trichlorobenzotrifluoride, 5 g of nitrobenzene and 25 g of CNC catalyst were added. The vessel was sealed and the mixture subsequently heated to 200° C. for 5 h and then to 220° C. for a further 12 h. During the reaction, a maximum total pressure of 9 bar arose. The mixture was then cooled to 20° C. and decompressed into a cooled receiver. The product was distilled off at standard pressure. After redistillation of the crude product, 300 g of 3,4,5-trifluorobenzotrifluoride (75percent of theory) were obtained as a colourless liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49% | In sulfolane; hexane; | (d) 1,3-Bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene A mixture of 3,4,5-trichloro-alpha,alpha,alpha-trifluorotoluene (10 g. 0.04 mol), and the dipotassium salt of 1,3-dihydroxybenzene (4 g. 0.021 mol) in 150 ml. sulfolane is stirred and heated 70 minutes at ~120 C. The cooled reaction mixture is diluted with benzene (350 ml.) and washed once with water (1 l). Hexane (200 ml.) is added, and the solution washed with water (3*500 ml.) dried, filtered through activated silica gel (~25 g.), and the solvents removed. The residual oil is crystallized from a mixture of pentane and benzene to give 1,3-bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene (5.3 g. 49%) m.p. 121-122 C. |
49% | In sulfolane; hexane; | (d) 1.3-Bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene A mixture of 3,4,5-trichloro-alpha,alpha,alpha-trifluorotoluene (10 g. 0.04 mol), and the dipotassium salt of 1,3-dihydroxybenzene (4 g. 0.021 mol) in 150 ml. sulfolane is stirred and heated 70 minutes at --120 C. The cooled reaction mixture is diluted with benzene (350 ml.) and washed once with water (1 l). Hexane (200 ml.) is added, and the solution washed with water (3*500 ml.) dried, filtered through activated silica gel (~25 g.), and the solvents removed. The residual oil is crystallized from a mixture of pentane and benzene to give 1,3-bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene (5.3 g. 49%) m.p. 121-122 C. |
49% | In sulfolane; hexane; | (d) 1,3-Bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene A mixture of 3,4,5-trichloro-alpha,alpha,alpha-trifluoro-toluene (10 g. 0.04 mol), and the dipotassium salt of 1,3-dihydroxybenzene (4 g. 0.021 mol) in 150 ml. sulfolane is stirred and heated 70 minutes at ~120 C. The cooled reaction mixture is diluted with benzene (350 ml.) and washed once with water (1 1). Hexane (200 ml.) is added, and the solution washed with water (3*500 ml.) dried, filtered through activated silica gel (~25 g.), and the solvents removed. The residual oil is crystallized from a mixture of pentane and benzene to give 1,3-bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene (5.3 g. 49%) m.p. 121-122 C. |
49% | In sulfolane; hexane; | d. 1,3-Bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene A mixture of 3,4,5-trichloro-alpha,alpha,alpha-trifluorotoluene (10 g. 0.04 mol), and the dipotassium salt of 1,3-dihydroxybenzene (4 g. 0.021 mol) in 150 ml. sulfolane is stirred and heated 70 minutes at ~120 C. The cooled reaction mixture is diluted with benzene (350 ml.) and washed once with water (1 L). Hexane (200 ml.) is added, and the solution washed with water (3*500 ml.) dried, filtered through activated silica gel (~25 g.), and the solvents removed. The residual oil is crystallized from a mixture of pentane and benzene to give 1,3-bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene (5.3 g. 49%) m.p. 121-122 C. |
49% | In sulfolane; hexane; | d. 1,3-Bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene A mixture of 3,4,5-trichloro-alpha,alpha,alpha-trifluorotoluene (10 g. 0.04 mol), and the dipotassium salt of 1,3-dihydroxybenzene (4 g. 0.021 mol) in 150 ml. sulfolane is stirred and heated 70 minutes at ~120 C. The cooled reaction mixture is diluted with benzene (350 ml.) and washed once with water (1 l). Hexane (200 ml.) is added, and the solution washed with water (3 * 500 ml.) dried, filtered through activated silica gel (~25 g.), and the solvents removed. The residual oil is crystallized from a mixture of pentane and benzene to give 1,3-bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyoxy)benzene (5.3 g. 49%) m.p. 121-122 C. |
49% | In sulfolane; hexane; | d. 1,3-Bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene A mixture of 3,4,5-trichloro-alpha,alpha,alpha-trifluorotoluene (10 g. 0.04 mol), and the dipotassium salt of 1,3-dihydroxybenzene (4 g. 0.021 mol) in 150 ml. sulfolane is stirred and heated 70 minutes at ~120 C. The cooled reaction mixture is diluted with benzene (350 ml.) and washed once with water (1 L). Hexane (200 ml.) is added, and the solution washed with water (3 * 500 ml.) dried, filtered through activated silica gel (~25 g.), and the solvents removed. The residual oil is crystallized from a mixture of pentane and benzene to give 1,3-bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene (5.3 g. 49%) m.p. 121-122 C. |
49% | In sulfolane; hexane; | d. 1,3-Bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene A mixture of 3,4,5-trichloro-alpha,alpha,alpha-trifluorotoluene (10 g. 0.04 mol), and the dipotassium salt of 1,3-dihydroxybenzene (4 g. 0.021 mol) in 150 ml. sulfolane is stirred and heated 70 minutes at ~120 C. The cooled reaction mixture is diluted with benzene (350 ml.) and washed once with water (1 1). Hexane (200 ml.) is added, and the solution washed with water (3 * 500 ml.) dried, filtered through activated silica gel (~25 g.), and the solvents removed. The residual oil is crystallized from a mixture of pentane and benzene to give 1,3-bis(2,6-dichloro-alpha,alpha,alpha-trifluoro-p-tolyloxy)benzene (5.3 g. 49%) m.p. 121-122 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.5%; 21.4% | With hydrogen fluoride; at 5 - 120℃; under 15001.5 Torr; for 2h;Product distribution / selectivity; | The mixture of benzotrichlorides from Example 1a is passed directly to the fluorination reactor, which consists of an AISI 316 steel autoclave equipped with a stirrer and connected via a valve for pressure control to the gaseous hydrogen chloride absorption system. Once the mixture of benzotrichlorides has been charged into the autoclave, it is cooled to 5 C and 25.5 mmol (510 g) of anhydrous hydrofluoric acid are added. While the mixture is subjected to vigorous stirring in such a manner as to permit the two phases to react, it is heated until it reaches a final temperature of 120 C which is maintained for 2 hours. The pressure within the autoclave is maintained at 20 bar by means of a control valve and the stream of gaseous HCl leaving the autoclave (15 mol, 547.5 g) is absorbed in water to produce 32% HCl for commercial use. When the production of gaseous HCl has ceased and the pressure remains constant, the reaction is complete. The temperature is lowered, stirring is stopped and the phases are separated in appropriate apparatus. The resultant organic phase (5 mol, 1133.5 g) is vacuum distilled to obtain 3.58 mol (768 g) of 3,4-dichlorobenzotrifluoride of a purity of 99.5% (yield 71.5%) and 1.07 mol (268 g) of 3,4,5-trichlorobenzotrifluoride of a purity of 99% (yield 21.4%). The remaining 98 g consist of 2,4,5-trichlorobenzotrifluoride and 2,3,4,5-tetrachlorobenzotrifluoride and remain as heavy bottoms products |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.2% | With 1-methyl-pyrrolidin-2-one; ammonia; at 0 - 190℃; for 8h; | 0.5 mol (124.7 g) of an 80:20 isomeric mixture consisting of <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> and 2,4,5-trichlorobenzotrifluoride and 1.8 mol (178 g) of N-methylpyrrolidone are introduced into an autoclave. The autoclave is cooled to 0C and charged with 4 mol of ammonia (68 g) and heated with vigorous stirring to 190C for 8 hours. After cooling and removal of excess ammonia, the reaction mixture is filtered off from the ammonium chloride produced and the liquid phase is vacuum distilled. The distillation yields 88.3 g of an azeotropic mixture containing 83% 2,6-dichloro-4-trifluoromethylaniline (2,6-DC-pTFMA) and 17% N-methylpyrrolidone. The 99% pure product is precipitated out from the azeotropic mixture by addition of water and, after filtration and drying, 0.317 mol (73 g) of 2,6-dichloro-4-trifluoromethylaniline (yield 79.2% relative to 3,4,5-TCBTF) are obtained. Examples 2 and 3 below are given in order to illustrate the advantage of keeping the conversion of 3,4-DCBTC into 3,4,5-TCBTC at a low level in the chlorination stage, in that if conversion of the 3,4-DCBTC is boosted, the result is not a greater yield of 3,4,5-TCBTC, but instead the formation of isomeric and polychlorinated products which require costly disposal |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.2% | With 1-methyl-pyrrolidin-2-one; ammonia; at 0 - 190℃; for 8h; | 0.5 mol (124.7 g) of <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> and 1.8 mol (178 g) of N-methylpyrrolidone are mixed in an autoclave. The autoclave is cooled to 0 C and charged with 4 mol of ammonia (68 g) and heated with vigorous stirring to 190 C for 8 hours. After cooling and removal of excess ammonia, the reaction mixture is filtered off from the ammonium chloride produced and the liquid phase is vacuum distilled. The distillation yields 110.4 g of an azeotropic mixture containing 83% 2,6-dichloro-4-trifluoromethylaniline and 17% N-methylpyrrolidone. The 99% pure product is precipitated out from the azeotropic mixture by addition of water and, after filtration and drying, 0.396 mol (91 g) of 2,6-dichloro-4-trifluoromethylaniline (yield 79.2%) are obtained. |
75.69% | With ammonia; In water; at 165℃; under 86258.6 Torr;Product distribution / selectivity; | Example 10-Example 19The unit and operation procedures are same to that of example 7, with results shown in Table 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With potassium fluoride; nitrobenzene;1,3-dimethyl-2-(N',N',N",N"-tetramethylguanidino)-4,5-dihydro-3H-imidazolium chloride; In sulfolane; at 200 - 220℃; under 6750.68 Torr; for 17h; | Example 3; Preparation method of 3,4,5-trifluorobenzotrifluoride; 860 g of dry sulpholane and 524 g of dry KF were initially charged with exclusion of moisture in an autoclave, and 500 g of <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong>, 5 g of nitrobenzene and 25 g of CNC catalyst were added. The vessel was sealed and the mixture subsequently heated to 200 C. for 5 h and then to 220 C. for a further 12 h. During the reaction, a maximum total pressure of 9 bar arose. The mixture was then cooled to 20 C. and decompressed into a cooled receiver. The product was distilled off at standard pressure. After redistillation of the crude product, 300 g of 3,4,5-trifluorobenzotrifluoride (75% of theory) were obtained as a colourless liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
<= 3.7% | With hydrazine; In tetrahydrofuran; at 50℃; for 24h;Product distribution / selectivity; | Comparative Example 1 : Preparation of 2,6-dichloro-4-(trifluoromethyl) phenylhydrazine of the formula 1-1 from 3,4,5-trichloro- benzotrifluoride in tetrahydrofurane; 10 g (40 mmole) of <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> (99.7% purity) were dissolved in 30 g (417 mmole) of tetrahydrofurane. To this solution were added 8 g (160 mmole) of <n="10"/>hydrazine hydrate (100%). The resulting mixture was stirred at 500C for 24 hours. Thereafter, an organic phase of 40.7 g was separated. The solution obtained by this separation contained the product 2,6-dichloro-4-(trifluoromethyl)phenylhydrazine in an amount of 0.9 wt-% and the starting material <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> in an amount of 27.1 wt-%, meaning that a product yield not higher than 3.7 % was obtained. |
<= 3.6% | With hydrazine; In toluene; at 110℃; for 24h;Product distribution / selectivity; | Comparative Example 3: Preparation of 2,6-dichloro-4-(trifluoromethyl)phenyl- hydrazine of the formula 1-1 from 3,4,5-trichloro- benzotrifluoride in toluene; 10 g (40 mmole) of <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> (99.7% purity) were dissolved in 30 g (326 mmole) of toluene. To this solution were added 8 g (160 mmole) of hydrazine hydrate (100%). The resulting mixture was stirred at reflux (approx. 1100C) for 24 hours. Thereafter, an organic phase of 39.4 g was separated. The solution obtained by this separation contained the product 2,6-dichloro-4-(trifluoromethyl)phenylhydrazine in an amount of 0.9 wt-% and the starting material <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> in an amount of 26.3 wt-%, meaning that a product yield not higher than 3.6 % was obtained. |
<= 2.5% | With hydrazine; In pyridine; at 25℃; for 24h;Product distribution / selectivity; | Comparative Example 2: Preparation of 2,6-dichloro-4-(trifluoromethyl)phenyl- hydrazine of the formula 1-1 from 3,4,5-trichloro- benzotrifluoride in pyridine (amount of hydrazine hydrate: 4 equivalents, reaction time: 24 hours, reaction temperature: 25C); 10 g (40 mmole) of <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> (99.7% purity) were dissolved in 30 g (380 mmole) of pyridine. To this solution were added 8 g (160 mmole) of hydrazine hydrate (100%). The resulting mixture was stirred at 25C for 24 hours. Thereafter, an organic phase of 41.6 g was separated (lower phase). The solution obtained by this separation contained the product 2,6-dichloro-4-(trifluoromethyl) phenylhydrazine in an amount of 0.5 wt-% and the starting material <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> in an amount of 26.4 wt-%, meaning that a product yield not higher than 2.5 % was obtained. |
With hydrazine hydrate; In pyridine; water; | 6.2 g (0.025 mol) of 3,4,5-trichloro-trifluoromethylbenzene and 6.25 g (0.125 mol) of hydrazine hydrate are heated under reflux for 48 hours at 115-120 C. in 12 ml of pyridine. For working up, the solvent is distilled off, and the residue is taken up in water and extracted three times with about 30 ml of dichloromethane each time. The combined organic phases are dried over magnesium sulphate and evaporated in vacuo, and the residue is then distilled. 5.1 g (83% of theory) of 2,6-dichloro-4-trifluoromethylphenylhydrazine of melting point 56 to 57 C. are obtained. STR954 | |
With hydrazine hydrate; In pyridine; dichloromethane; water; | 6.2 g (0.025 mole) of 3,4,5-trichloro-trifluoromethylbenzene and 6.25 g (0.125 mole) of hydrazine hydrate are heated under reflux in 12 ml of pyridine at 115-120 C. for 48 hours. For working up, the solvent is distilled off, the residue is taken up in water and the mixture is extracted three times with in each case about 30 ml of methylene chloride. The combined organic phases are dried over magnesium sulphate, concentrated in vacuo and then distilled. 5.1 g (83% of theory) of 2,6-dichloro-4-trifluoromethylphenylhydrazine of melting point 56 to 57 C. are obtained. The following 1-aryl-5-hydrazino-pyrazoles of the formula (I) are obtained in a corresponding manner and in accordance with the general statements on the preparation: STR59 | |
With hydrazine hydrate; In pyridine; water; | 6.2 g (0.025 mol) of 3,4,5-trichloro-trifluoromethylbenzene and 6.25 g (0.125 mol) of hydrazine hydrate are refluxed at 115-120 C. for 48 hours in 12 ml of pyridine. For work-up, the solvent is removed by distillation, and the residue is taken up in water and extracted three times with about 30 ml of dichloromethane in each case. The combined organic phases are dried over magnesium sulphate, concentrated in vacuo and subsequently distilled. 5.1 g (83% of theory) of 2,6-dichloro-4-trifluoromethylphenylhydrazine of melting point 56 to 57 C. are obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In Petroleum ether; | EXAMPLE (II-1) STR36 12.5 g (0.05 mol) of 3,4,5-trichloro-benzotrifluoride are added slowly to a stirred mixture, heated to 60 C., of 8.0 g (0.05 mol) of 2,7-dihydroxy-naphthalene, 4.2 g (0.075 mol) of potassium hydroxide powder and 100 ml of dimethyl sulphoxide, and stirring of the reaction mixture is continued for approximately 3 hours at 60 C. After the mixture has cooled to approximately 20 C., it is diluted with water and methylene chloride and filtered. The organic phase is separated from the filtrate, washed with water, dried using sodium sulphate and filtered. The solvent is distilled off from the filtrate under a waterpump vacuum, the residue is stirred with petroleum ether, and the product which is obtained in this process in the form of crystals is isolated by filtering off with suction. 4.9 g (26% of theory) of 7-(2,6-dichloro-4-trifluoromethyl-phenoxy)-2-naphthol of melting point 98 C. are obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step 1 (VII-1): STR29 124 g (0.5 mol) of <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> are added to a stirred mixture of 135 g (0.5 mol) of the sodium salt of 6-hydroxy-naphthalene-2-sulphonic acid, 30 g (0.54 mol) of potassium hydroxide powder and 1,000 ml of dimethyl sulphoxide, and the reaction mixture is stirred first for 3 hours at 60 C. and then for 15 hours at 20 C. After the mixture has been concentrated, the residue is digested with water, and the product which has been obtained in crystalline form is isolated by filtration with suction. This gives 209.5 g (91% of theory) of the sodium salt of 6-(2,6-dichloro-4-trifluoromethyl-phenoxy)-naphthalene-2-sulphonic acid, which melts above 310 C. with decomposition. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; | STR66 46.8 g (0.19 mole) of 3,4,5-trichloro-benzotrifluoride are added slowly and with stirring to a mixture which consists of 56.8 g (0.36 mole) of 2,6-dihydroxynaphthalene, 14.3 g (0.36 mole) of pulverulent sodium hydroxide and 170 ml of dimethyl sulphoxide and which has been heated to 120 C., and the reaction mixture is then stirred at 120 C. for approximately 3 hours and further at 20 C. for approximately 15 hours. The reaction mixture is then diluted with water to twice the volume, and acidified with 1N hydrochloric acid. The precipitate obtained is separated off and extracted with toluene, and the organic phase is separated off, washed with water, dried over sodium sulphate and filtered. The solvent is distilled off the filtrate in a waterpump vacuum. The residue is recrystallized from ethanol. 52 g (74% of theory) of 6-(2,6-dichloro-4-trifluoromethyl-phenoxy)-2-naphthol of melting point 158 C. are obtained. The starting substances of the formula (II) listed in Table 2 below can be prepared in analogy with Example (II-1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; In Petroleum ether; | STR73 12.5 g (0.05 mol) of 3,4,5-trichloro-benzotrifluoride are added slowly and with stirring to a mixture of 8.0 g (0.05 mol) of 2,7-dihydroxynaphthalene, 4.2 g (0.075 mol) of pulverulent potassium hydroxide and 100 ml of dimethyl sulphoxide, which has been warmed to 60 C., and the reaction mixture is then stirred for a further approx. 3 hours at 60 C. After the mixture has been cooled to approximately 20 C., it is diluted with water and methylene chloride, and filtered. The organic phase is separated off from the filtrate, washed with water, dried using sodium sulphate and filtered. The solvent is removed from the filtrate by distillation in a water-pump vacuum, the residue is stirred with petroleum ether and the product which is thus obtained in the form of crystals is isolated by filtering with suction. 4.9 g (26% of theory) of 7-(2,6-dichloro-4-trifluoromethylphenoxy)-2-naphthol of melting point 98 C. are obtained. In analogy to Example (II-1) the starting substances of the formula (II) listed below in Table 2 may be prepared. STR74 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; | PRODUCTION EXAMPLE 3 (Production of Compound No. (3)) After 44 mg (1.1 mmol) of 60% sodium hydride was added to a solution of 0.14 g (1 mmol) of 5-(1-methylcyclopropyl)-1,3,4-oxadiazolin-2-one in 5 ml of N,N-dimethylformamide at room temperature, the mixture was stirred at the same temperature for 15 minutes. To the mixture was added 0.25 g (1 mmol) of <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> followed by heating a 80 C. for 6 hours. After cooling, the mixture was poured into water and extracted with ethyl acetate. After drying over magnesium sulfate, the extract was concentrated under reduced pressure to give the crude product. The crude product was subjected to silica gel column chromatography to give 35 mg of 5-(1-methylcyclopropyl)-3-(2,6-dichloro-4-trifluoromethylphenyl)-1,3,4-oxadiazoline-2-one. m.p. 107.1 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With calcium hydroxide; In water; dimethyl sulfoxide; | (a) Preparation by the process according to the invention 358 g (1.5 mol) of <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> were added dropwise to a mixture of 330 g (3 mol) of resorcinol and 111 g (1.5 mol) of calcium hydroxide in 2 liters of dimethylsulfoxide at 120-130 C. in the course of 7 hours. Thereafter, the reaction mixture was stirred at 130 C. for 8 hours. After cooling to room temperature, the reaction mixture was poured into 7 liters of water, whereupon the reaction product separated out as an oil. The mixture was extracted with 3 liters of toluene and the organic phase was separated off and, after drying, was concentrated. The residue was distilled. 350 g (73% of theory) of 2,6-dichloro-4-trifluoromethyl-3'-hydroxydiphenyl ether were obtained in this manner in the form of a solid product of melting point 64-65 C. Boiing point 123-130 C./0.15 mm Hg Analysis: Empirical formula: C13 H7 Cl2 F3 O2: Calculated: 48.3% C; 2.2% H; 22.0% Cl. Found: 48.3% C; 2.3% H; 21.8% Cl. | |
With sodium hydroxide; In water; dimethyl sulfoxide; toluene; | (b) Preparation by a known process, using sodium hydroxide as the base 358 g (1.5 mol) of 3,4,5-trichloro-benzotrifluoride were added dropwise to a mixture of 330 g (3 mol) of resorcinol and 60 g (1.5 mol) of sodium hydroxide in 2 liters of dimethylsulphoxide at 120-130 C. in the course of 7 hours. Thereafter, the reaction mixture was stirred at 130 C. for 8 hours. After cooling to room temperature, the reaction mixture was stirred into a solution of 80 g of sodium hydroxide in 7 liters of water. The insoluble portion was separated off and taken up in toluene; according to the thin layer chromatogram, this solution contained no 2,6 -dichloro-4-trifluoromethyl-3'-hydroxydiphenyl ether. In order to work up the aqueous phase, it was acidified with hydrochloric acid and the oil which separated out was extracted with toluene. After drying, the solvent was stripped off and the residue was distilled. 30 g (6.7% of theory) of 2,6-dichloro-4-trifluoromethyl-3'-hydroxydiphenyl ether were obtained in this manner. Boiling point 123-130 C./0.15 mm Hg. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium nitrite;copper(I) chloride; In hydrogenchloride; water; | (b) Preparation of 3,4,5-trichlorobenzotrifluoride 2,6-Dichloro-4-trifluoromethylaniline (3.3 kg) in concentrated hydrochloric acid (25 liters) was stirred for 1 hour and then cooled to -6 C. A solution of sodium nitrite (1.41 kg) in water (3 liters) was added over a period of 4 hours keeping the temperature between -5 and -12. The mixture was then stirred between -5 and 0 until all solid had dissolved (3.5 hours). The mixture was then added in 2 liter portions over a period of 35 minutes to a solution of cuprous chloride (1.5 kg) in concentrated hydrochloric acid with stirring. The dark solution was left to stand for 30 minutes, filtered, and extracted with dichloromethane (1*15 liters, then 2*10 liters). The extracts were washed with water (2*25 liters) dried (MgSO4) and evaporated under reduced pressure to give 3,4,5-trichlorobenzotrifluoride (2.2 kg) with a boiling range of 98- 100/40 Torr. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium nitrite;copper(I) chloride; In dichloromethane; water; | (b) Preparation of 3,4,5-trichlorobenzotrifluoride from 4-chloro-3,5-diaminobenzotrifluoride Concentrated hydrochloric acid (75 liters) was cooled to -20 C. and stirred while a solution of sodium nitrite (10.5 kg) in water (22.5 liters) and a solution of 4-chloro-3,5-diaminobenzotrifluoride (7.5 kg) in dichloromethane (22.5 liters) were both slowly added. The total time taken for addition was 6 hours. The temperature of the mixture was kept between -12 and -6. The mixture was stirred for a further 30 minutes at between -6 and -9, and then transferred slowly on to a mixture of cuprous chloride (7 kg) and concentrated hydrochloric acid (40 liters), kept at a temperature between 13 and 23 by water-cooling. The mixture was then stirred for about 90 minutes at 15. The dichloromethane layer was separated and the aqueous layer re-extracted with more dichloromethane (2*20 liters). The combined dichloromethane extracts were washed with water (3*30 liters) and then evaporated leaving an oil (6.06 kg). This was distilled (some material lost by spillage) at a pressure of 30 Torr to give the required 3,4,5-trichlorobenzotrifluoride (boiling range 84-92). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With sodium nitrite;copper(I) chloride; In hydrogenchloride; water; | (c) 3,4,5-Trichloro-alpha,alpha,alpha-trifluorotoluene A solution of sodium nitrite (39 g.) in water (85 ml.) is added over 1 hour to a solution of 5-amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene (117.5 g., 0.51 mol) in 1700 ml. concentrated hydrochloric acid at -6 C. and the solution stirred for 1 hour then filtered. The filtrate is added to a solution of cuprous chloride (76.5 g.) in concentrated hydrochloric acid (500 ml.) over 5 minutes at 0 to 8 C. and gradually heated to 80 C. over 80 minutes. The reaction mixture is cooled to 35 C. and extracted with hexane (2*300 ml.). The extract is washed with water, 2% sodium hydroxide solution, dried and distilled to give 3,4,5-trichloro-alpha,alpha,alpha-trifluorotoluene (70 g., 55%) b.p. 82-86 C./10 mm, 95% pure. |
55% | With sodium nitrite;copper(I) chloride; In hydrogenchloride; water; | (c) 3,4,5-trichloro-alpha,alpha, alpha-trifluorotoluene A solution of sodium nitrite (39 g.) in water (85 ml.) is added over 1 hour to a solution of 5-amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene (117.5 g., 0.51 mol) in 1700 ml. concentrated hydrochloric acid at -6 C. and the solution stirred for 1 hour then filtered. The filtrate is added to a solution of cuprous chloride (76.5 g.) in concentrated hydrochloric acid (500 ml.) over 5 minutes at 0 to 8 C. and gradually heated to 80 C. over 80 minutes. The reaction mixture is cooled to 35 C. and extracted with hexane (2*300 ml.). The extract is washed with water, 2% sodium hydroxide solution, dried and distilled to give 3,4,5-trichloro-alpha,alpha,alpha-trifluorotoluene (70 g., 55%) b.p. 82-86 C./10 mm, 95% pure. |
55% | With sodium nitrite;copper(I) chloride; In hydrogenchloride; water; | c. 3,4,5-Trichloro-alpha,alpha,alpha-trifluorotoluene A solution of sodium nitrite (39 g.) in water (85 ml.) is added over 1 hour to a solution of 5-amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene (117.5 g., 0.51 mol) in 1700 ml. concentrated hydrochloric acid at -6 C. and the solution stirred for 1 hour then filtered. The filtrate is added to a solution of cuprous chloride (76.5 g.) in concentrated hydrochloric acid (500 ml.) over 5 minutes at 0 to 8 C. and gradually heated to 80 C. over 80 minutes. The reaction mixture is cooled to 35 C. and extracted with hexane (2*300 ml.). The extract is washed with water, 2% sodium hydroxide solution, dried and distilled to give 3,4,5-trichloro-alpha,alpha,alpha-trifluorotoluene (70 g., 55%) b.p. 82-86 C./10 mm, 95% pure. |
55% | With sodium nitrite;copper(I) chloride; In hydrogenchloride; water; | c. 3,4,5-Trichloro-alpha,alpha,alpha-trifluorotoluene A solution of sodium nitrite (39 g.) in water (85 ml.) is added over 1 hour to a solution of 5-amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene (117.5 g., 0.51 mol) in 1700 ml. concentrated hydrochloric acid at -6 C. and the solution stirred for 1 hour then filtered. The filtrate is added to a solution of cuprous chloride (76.5 g.) in concentrated hydrochloric acid (500 ml.) over 5 minutes at 0 to 8 C. and gradually heated to 80 C. over 80 minutes. The reaction mixture is cooled to 35 C. and extracted with hexane (2 * 300 ml.). The extract is washed with water, 2% sodium hydroxide solution, dried and distilled to give 3,4,5-trichloro-alpha,alpha,alpha-trifluorotoluene (70 g., 55%) b.p. 82-86 C./10 mm, 95% pure. |
55% | With sodium nitrite;copper(I) chloride; In hydrogenchloride; water; | c. 3,4,5-Trichloro-alpha,alpha,alpha-trifluorotoluene A solution of sodium nitrite (39 g.) in water (85 ml.) is added over 1 hour to a solution of 5-amino-3,4-dichloro-alpha,alpha,alpha-trifluorotoluene (117.5 g., 0.51 mol) in 1700 ml. concentrated hydrochloric acid at -6 C. and the solution stirred for 1 hour then filtered. The filtrate is added to a solution of cuprous chloride (76.5 g.) in concentrated hydrochloric acid (500 ml.) over 5 minutes at 0 to 8 C. and gradually heated to 80 C. over 80 minutes. The reaction mixture is cooled to 35 C. and extracted with hexane (2 * 300 ml.). The extract is washed with water, 2% sodium hydroxide solution, dried and distilled to give 3,4,5-trichloro-alpha,alpha,alpha--trifluorotoluene (70 g., 55%) b.p. 82-86 C./10 mm, 95% pure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dimethyl sulfoxide; | EXAMPLE 3 - Preparation of 2,6-dichloro-4-trifluoromethyl-3'-methoxy-4'-cyano-diphenyl-ether SPC13 2,6-Dichloro-4-trifluoromethyl-3'-methoxy-4'-cyano-diphenyl-ether was prepared analogously to Example 2; it boiled at a boiling point (3 mm Hg) of 174C and melted at 140C after recrystallization from methanol. 2,6-Dichloro-4'-bromo-4-trifluoromethyl-3'-methoxy-diphenyl-ether (boiling point, 3: 166C, nD23: 1.5678) required as the starting material, was obtained according to process variant (b) by bromination of 2,6-dichloro-4-trifluoromethyl-3'-methoxy-diphenyl-ether. 2,6-Dichloro-4-trifluoromethyl-3'-methoxy-diphenyl-ether was obtained according to process variant (a) from sodium 3-methoxyphenolate and <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> in dimethylsulfoxide at 120C (boiling point, 3: 150C; nD23: 1.5438). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dimethyl sulfoxide; | EXAMPLE 1 - Preparation of 2,6-dichloro-4-trifluoromethyl-4'-cyanodiphenyl-ether SPC11 143 g (1 mol) of p-cyanophenol sodium were dissolved in 600 ml of dimethylsulfoxide. 250 g (1 mol) of <strong>[50594-82-6]3,4,5-trichlorobenzotrifluoride</strong> were added thereto and the mixture was warmed to 140C for six hours. After cooling, the solvent was distilled off almost completely in vacuo, and the residue was poured onto ice water. The precipitated product was extracted twice with 400 ml of methylene chloride. The organic phase was separated off, washed repeatedly with water and once with 200 ml of 20% strength sodium hydroxide solution. After drying over sodium sulfate, the solvent was removed in vacuo, and the oily residue was triturated with methanol, whereupon it crystallized and, after filtering off, was recrystallized from methanol. 166 g of 2,6-dichloro-4-trifluoromethyl-4'-cyanodiphenyl-ether of melting point 124C were obtained representing 50% of theory. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium fluoride;tetraphenylphosphonium bromide; In sulfolane; at 100 - 190℃; under 75.0075 Torr; for 15h;Product distribution / selectivity; | Example 1 : Preparation of a mixture comprising 1 ,3-dichloro-2-fluoro-5- trifluoromethylbenzene of the formula Il and 1 ,2-dichloro-3-fluoro-5- trifluoromethylbenzene of the formula III; 23 g (0.396 mol) KF, 12.8 g (0.03 mol) PPh4Br, 91.2 g sulfolane and 152 ml toluene were mixed in a 500 ml reactor. Toluene was distilled off under reduced pressure(1400C, thetaOmbar; aceotropic removal of water). After cooling to 1000C, 76 g (0.305 mol) 1 ,2,3-trichloro-5-trifluoromethylbenzene were added and the resulting mixture was heated at 190C for 15 h under reduced pressure (100 mbar). The mixture of 1 ,3- dichloro-2-fluoro-5-trifluoromethylbenzene and 1 ,2-dichloro-3-fluoro-5- trifluoromethylbenzene was distilled off simultaneously via a column. Two distillation fractions were obtained, which contained 31 % GC area-% of the product mixture, 1 % GC area-% of difluoro compounds and 6.6% GC area-% of the educt 1 ,2,3-trichloro-5- trifluoromethylbenzene. The identity of the mixture was determined by GC/MS spectrometry and 19F-NMR spectroscopy. | |
0.04 - 4.2%Chromat.; 0.15 - 14.2%Chromat. | With tetraphenylphosphonium hydrogendifluoride; for 2h;Heating / reflux;Product distribution / selectivity; | Comparative Example 1 : Reaction of 1 ,2,3-trichloro-5-trifluoromethylbenzene (3,4,5- trichlorobenzotrifluoride) with tetraphenylphosphonium hydrogen difluoride (tetraphenylphosphonium bifluoride); 1.12 g (0.0029 mol) of tetraphenylphosphonium hydrogen difluoride were added to 8.08 g (0.03 mol) of 1 ,2,3-trichloro-5-trifluoromethylbenzene and the resulting mixture was heated under reflux for 2 hours. The reaction mixture was allowed to cool and solved in water. The products were extracted with methyl tert-butylether. The conversion was determined by gas-chromatographic analysis. 0.15 GC area-% of 1 ,3- dichloro-2-fluoro-5-trifluoromethylbenzene of the formula II, 0.04 GC area-% of 1 ,2- dichloro-3-fluoro-5-trifluoromethylbenzene of the formula III, and 91.06% GC area-% of the educt 1 ,2,3-trichloro-5-trifluoromethylbenzene were obtained.; Comparative Example 2: Reaction of 1 ,2,3-trichloro-5-trifluoromethylbenzene (3,4,5- trichlorobenzotrifluoride) with tetraphenylphosphonium hydrogen difluoride (tetraphenylphosphonium bifluoride) employing a 1 :1 stoichiometry of the reactants; 1.12 g (0.0029 mol) of tetraphenylphosphonium hydrogen difluoride were added to 0.75 g (0.003 mol) of 1 ,2,3-trichloro-5-trifluoromethylbenzene and the resulting mixture was heated under reflux for 2 hours. The reaction mixture was allowed to cool and solved in water. The products were extracted with methyl tert-butylether. The conversion was determined by gas-chromatographic analysis. 14.2 GC area-% of 1 ,3- dichloro-2-fluoro-5-trifluoromethylbenzene of the formula II, 4.2 GC area-% of 1 ,2- dichloro-3-fluoro-5-trifluoromethylbenzene of the formula III, and 44.6 GC area-% of the educt 1 ,2,3-trichloro-5-trifluoromethylbenzene were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.46%; 12.29%; 5.25% | With sulfuric acid; chlorine;aluminum (III) chloride; iron; at 110℃;Product distribution / selectivity; | Into a 1000 ml 4-neck flask add p-chloro trifluoromethyl benzene 1000 g, metal powdered iron 6 g, and anhydrous aluminum chloride 10 g, start agitation, heat the mixed solution to 100 C., then slowly feed concentrated sulfuric acid-dried chlorine 1028 g under reaction temperature 110 C., take sample, make GC analysis and trace to judge the reaction end point, lower the temperature, discharge the products, and obtain mixed solution of chlorides. The mixed solution contains 82.46% the 3,4-dichlorotrifluoromethyl benzene, 5.25% the 3,4,5-trichloro trifluoromethyl benzene and 12.29% 2,4,5-trichloro trifluoromethyl benzene and polychlorides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen fluoride; at 110℃; under 11251.1 - 12751.3 Torr; | pressurize the mixture of 3,4-dichlorotrichlorotoluene and 3,4,5-trichlorotrichlorotoluene obtained from the previous reaction and 12 moles of anhydrous hydrogen fluoride into a 3L reactor, check each Opening condition of the valve.Turn on the stirring, and slowly introduce steam into the jacket. When the pressure in the kettle reaches 1.5MPa, open the exhaust gas discharge valve and continue to heat up until the temperature in the kettle is 110 C. At the same time, control the pressure in the kettle from 1.5 to 1.7MPa. When the pressure in the kettle no longer rises, the sample is analyzed. When the content of 3,4,5-trichlorotrifluorotoluene reaches 8-10%, the exhaust gas discharge valve is opened to release the pressure.After the pressure relief is completed, dry air is introduced into the reaction kettle to discharge unreacted hydrogen fluoride, hydrogen chloride gas and gas impurities generated in the reaction kettle to obtain 3,4-dichlorotrifluorotoluene and 3,4,5-trichloro Trifluorotoluene mixture.(3) Distillation: Under the condition of reflux ratio of 5: 2, the mixture obtained in the second step rectifies 3,4-dichlorotrifluorotoluene to form a concentrate containing 3,4,5-trichlorotrifluorotoluene. The residue was distilled, and then rectification was repeated. The fractions with a gas phase temperature of 199 to 202 C. at the top of the column were collected, and the target compound was obtained after condensation.Generally, the first rectification can reach 70-78%, and the second rectification can reach more than 96%.(4) Neutralization packaging: transfer 3,4,5-trichlorotrifluorotoluene with a purity of more than 96wt% to a neutralization kettle, add a certain amount of soda ash, turn on the stirring to neutralize it to neutral pH, and then filter Packaging 3,4,5-trichlorotrifluorotoluene finished product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With chlorine; at 95 - 110℃; for 24h; | (1) Chlorination: Put 800g of p-chlorotrifluorotoluene into a 3L reactor, and raise the temperature to 95 C. Add 40g of catalyst, and pass in dry chlorine gas with a flow rate of 40-80 m3/h, after 4 hours of reaction, the temperature was increased to 110C, and chlorine was passed through for 20 hours until the reaction was completed. Pass in dry air to exhaust unreacted chlorine gas in the reaction kettle, hydrogen chloride gas and gas impurities produced by the reaction, to obtain a mixture of 3,4-dichlorotrifluorotoluene and 3,4,5-trichlorotrifluorotoluene; (2) Distillation: Under the condition of reflux ratio of 5: 2, after the mixture obtained in the first step is distilled from 3,4-dichlorotrifluorotoluene, a distillation residue containing 3,4,5-trichlorotrifluorotoluene is formed, thereafter, the distillation was repeated, and a fraction with a gas phase temperature of 199 to 202 C. At the top of the column was collected. The target compound was obtained after condensation. Generally the first rectification can reach 70-78%, the second rectification can reach more than 96%; (3) Neutralization packaging: transfer 3,4,5-trichlorotrifluorotoluene with a purity of more than 96wt% to a neutralization kettle, add a certain amount of soda ash, start stirring and neutralize to a neutral pH, and then filter, the finished 3,4,5-trichlorotrifluorotoluene is then packaged. |
Tags: 50594-82-6 synthesis path| 50594-82-6 SDS| 50594-82-6 COA| 50594-82-6 purity| 50594-82-6 application| 50594-82-6 NMR| 50594-82-6 COA| 50594-82-6 structure
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P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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