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CAS No. : | 1513-65-1 |
Formula : | C5H3F2N |
M.W : | 115.08 |
SMILES Code : | FC1=CC=CC(F)=N1 |
MDL No. : | MFCD00006227 |
InChI Key : | MBTGBRYMJKYYOE-UHFFFAOYSA-N |
Pubchem ID : | 73934 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H225-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅲ |
* 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 |
---|---|---|
In sulfuric acid; | STEP A: 2,6-difluoro-3-nitropyridine To a stirred solution of 20 g. of 2,6-difluoropyridine in 100 ml. of concentrated sulfuric acid at about 20 C., was added 75 ml. of 90% fuming nitric acid over 20 minutes. The mixture was kept at room temperature overnight, warmed to 35 C. over 15 minutes and held at this temperature for 10 minutes. The solution was cooled and poured into ice. The oil was extracted with 400 ml. of ether and the ether extract was washed with bicarbonate solution until all of the acid was neutralized. The ether was dried, evaporated and the residue was distilled at 0.1 mm. The only fraction came over at 50 C. | |
With dihydrogen peroxide; nitric acid; at 0 - 60℃; for 3h; | To a solution of 2,6-difluoropyridine (5.00 g, 43.4 mmol) in Conc.HN03 (36.3 mL, 869 mmol) was added concentrated H2S04 (34.7 mL, 652 mmol) slowly at 0 C and the reaction mixture was heated at 60 C for 3h. Progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled at room temperature, poured into crushed ice (120 mL) and extracted with DCM (2 c 100 mL). The organic layer was separated, washed with an aqueous saturated NaHC03 solution (120 mL), dried over anhydrous Na2S04 and concentrated under vacuum to afford 2,6-difluoro-3-nitropyridine X-12a (3.20 g crude) as a yellow oil. (0877) This compound was used as such for the next reaction without further purification. 1 H NMR (400 MHz, DMSO-cfe) d 7.47 (dd, J=8.80, 2.45 Hz, 1 H) 8.91 -9.00 (m, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.9% | To a solution of 2,6-difluoropyridine (25.0 g, 217 mmol) in tetrahydrofuran (300 ml) was added dropwise 1.6 N n-butyllithium-hexane solution (163 ml) at -70 C., and the mixture was stirred at -70 C. for 1 hr. Dry ice (14.5 g, 330 mmol) was added at -70 C., and the mixture was stirred at -70 C. for 30 min, and then under ice-cooling for 1 hr. The reaction mixture was poured into ice water, and washed with ethyl acetate. The aqueous layer was adjusted to pH=3 with 3N hydrochloric acid, and extracted with ethyl acetate. The extract was washed with water, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was recrystallized from a mixed solvent of diethyl ether and hexane to give the object product (21.7 g, 62.9%) as a solid. 1H-NMR (CDCl3) δ; 6.89-6.94 (1H, m), 8.48-8.57 (1H, m). | |
Synthesis of 2,6-difluoronicotinic acid A 2.62 M solution of n-butyllithium in THF (29.1 mL) was added dropwise to a solution of diisopropylamine (11.7 mL) in tetrahydrofuran (310 mL) under ice-cooling in a nitrogen atmosphere, and the reaction solution was stirred under ice-cooling for one hour. After cooling the reaction solution to -78C, a solution of 2,6-difluoropyridine [CAS# 1513-65-1] (8 g) in tetrahydrofuran (10 mL) was added dropwise to the reaction solution, and the reaction solution was stirred at -78C for three hours. Then, an excessive amount of crushed dry ice was added to the reaction solution in a nitrogen stream, and the reaction solution was stirred at -78C for 20 minutes and at room temperature for three hours. Water and diethyl ether were added to the reaction solution, and the aqueous layer was separated. The aqueous layer was adjusted to pH 1 with concentrated hydrochloric acid. Then, ethyl acetate was added and the organic layer was separated. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 10.4 g of a crude product of the title compound. The property values of the compound are as follows. 1H-NMR (CD3OD) δ (ppm): 7.08 (dd, J = 8.4, 2.8 Hz, 1H) 8.58 (dd, J = 17.2, 8.4 Hz, 1H). | ||
To a stirring -78 0C solution of LDA (91.34 ml of 1.8 M in heptane/THF/ethylbenzene, 164.41 mmol) and TBDF (201 ml) was added slowly over 20 min. a solution of 2,6- difluoropyridine (18.92 g, 164.41 mmol) in THF (20 ml) so that the internal temperature stayed below -70 0C. After the addition, the reaction was stirred for 3 h at -78 0C. Dry ice (about 22 g) was treated with a stream of N2 gas before being added to the mixture over a 5 min. period. The internal temperature rose to -50 0C as a result of an exothermic reaction. Once the internal temperature stabilized back to -78 0C, it was stirred for 30 min before being gradually warmed to RT arid then stirred for 18 h. The solution was acidified to pH 2.5 with HCl (10% aqueous solution). The organic solvents were removed under vacuum, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, decanted, and concentrated under vacuum. The crude was treated with cold Et2O. The beige solid was isolated by filtration and washed twice with small amounts of cold diethyl ether to yield title compound. |
12.3 ml of N,N-diisopropylamine was mixed with 100 ml of THF. Thereafter, 50 ml of a hexane solution containing 1.6 mol/liter n-butyllithium was mixed therewith at -78C. The obtained mixture was stirred at -78C for 20 minutes. Thereafter, 10.1 g of 2,6-difluoropyridine dissolved in 50 ml of THF was added to the reaction mixture at -78C over 10 minutes. The obtained mixture was stirred for 30 minutes. Thereafter, dry ice was added to the reaction mixture, and the obtained mixture was stirred for 4 hours, while the temperature thereof was gradually raised to a room temperature. Thereafter, water was added to the reaction mixture, followed by partition with MTBE. Subsequently, concentrated hydrochloric acid was added to the water layer, so that the pH thereof was adjusted to pH 1, followed by extraction with ethyl acetate. The organic layer was washed with a saturated saline solution, and it was then dried over sodium sulfate, followed by concentration under reduced pressure. The obtained residue was washed with a mixed solvent of hexane and MTBE, so as to obtain 8.69 g of 2,6-difluoronicotinic acid.2,6-difluoronicotinic acid [Show Image] 1H-NMR (DMSO-D6) δ: 7.30 (1H, dd, J = 8.2, 2.4 Hz), 8.59 (1H, dd, J = 8.2, 4.1 Hz). | ||
Example 8; Synthesis of Aldehyde ReagentsAldehyde reagents that are used in making compounds are prepared according to the following protocols. In these reactions, the unprotected aldehyde isolated after step 5, or the subsequently Boc-protected aldehyde may be used in preparation of compounds.(6-ethoxy-pyridin-3-yl)-(6-fluoro-5-formyl-pyridin-2-yl)-carbamic acid tert-butyl ester 57 is prepared in six steps from 2,6-difluoro-pyridine 39 as shown in Scheme 8. Step 1-Preparation of 2,6-difluoro-nicotinic acid (51)In a round bottom flask, to 2,6-difluoro-pyridine (39, 7.10 g, 61.7 mmol) in 150.0 mL of tetrahydrofuran under an atmosphere of nitrogen at -78 C., n-butyllithium (26.0 mL, 2.50 M in hexane, 65.0 mmol) is slowly added. After 30 minutes, 3.0 g of dry ice is added and an hour later the reaction is allowed to warm to room temperature. The reaction is poured into water, extracted with ethyl acetate and the aqueous layer is adjusted to pH 4-5 with 1 N hydrochloric acid. This is extracted with ethyl acetate and the organic layer is dried over sodium sulfate, filtered and the filtrate concentrated under vacuum to provide the desired compound (51, 5.6 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With ammonia; In water; at 105℃; for 15h; | Example 13: (4S)-Λ/-Methyl-Λ/-(f5-(4-methyl-1-piperazinvnimidazoϖ .2-aloyridin-2- vϖmethyl)-3,4-dihvdro-2H-pyranof3,2-b1pyridin-4-arnine EPO <DP n="41"/>A) 6-Fluoro-2-pyridinamine: A solution of 2,6-difluoropyridine (50 g, 434 mmol) in ammonium hydroxide (200 mL, 28.0- 30.0%) was heated at 1050C in a steel bomb for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with cold water, and dried to yield 6-fluoro-2- pyridinamine (45.8 g, 94% yield) as a white solid. 1H-NMR (CDCI3): δ 7.53 (m, 1 H)1 6.36 (dd, 1 H), 6.26 (dd, 1 H), 4.56 (s, 2H). |
94% | With ammonia; In water; at 105℃; for 15h; | A solution of 2,6-difluoropyridine (50 g, 434 mmol) in ammonium hydroxide (200 mL, 28.0-30.0%) was heated at 1050C in a steel bomb for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with cold water, and dried to yield 6-fluoro-2-pyridinamine (45.8 g, 94% yield) as a white solid. 1H-NMR (CDCI3): δ 7.53 (m, 1H), 6.36 (dd, 1H), 6.26 (dd, 1H), 4.56 (s, 2H). |
94% | With ammonia; In water; at 105℃; for 15h; | A solution of 2,6-difluoropyridine (50 g, 434 mmol) in ammonium hydroxide (200 mL, 28.0-30.0%) was heated at 1050C in a steel bomb for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with cold water, and dried to yield 6-fluoro-2-pyridinamine (45.8 g, 94% yield) as a white solid. 1H-NMR (CDCI3): δ 7.53 (m, 1 H), 6.36 (dd, 1 H), 6.26 (dd, 1 H), 4.56 (s, 2H). |
94% | With ammonia; In water; at 105℃; for 15h; | A solution of 2,6-difluoropyridine (50 g, 434 mmol) in ammonium hydroxide (200 ml_, 28.0-30.0%) was heated at 1050C in a steel bomb for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with cold water, and dried to yield 6-fluoro-2-pyridinamine (45.8 g, 94% yield) as a white solid. 1H-NMR (CDCI3): δ 7.53 (m, 1 H)1 6.36 (dd, 1 H), 6.26 (dd, 1 H), 4.56 (s, 2H). |
94% | With ammonia; In water; at 105℃; for 15h; | A solution of 2,6-difluoropyridine (50 g, 434 mmol) in ammonium hydroxide (200 mL, 28.0-30.0%) was heated at 1050C in a steel bomb for 15 hours. The reaction was cooled in an ice bath and the precipitate filtered, rinsed with cold water, and dried to yield 6-fluoro-2-pyridinamine (45.8 g, 94% yield) as a white solid. 1H-NMR (CDCI3): δ 7.53 (m, 1H), 6.36 (dd, 1H), 6.26 (dd, 1H), 4.56 (S1 2H). |
92% | With ammonium hydroxide; In water; at 110℃; | 2-(chloromethyl)-5-fluoroimidazoH ,2-alpyridine: 2,6-difluoropyridine (31.5 ml_, 0.348 mol) was diluted with 30% ammonium hydroxide(20OmL) in a steel bomb and heated to 110s C overnight. The bomb was cooled to room temperature over two hours then further cooled to 0Q C for two hours. The resulting solid was filtered and rinsed with water to obtain 26.39 g as a white solid. The filtrate was extracted with dichloromethane, dried over sodium sulfate and concentrated to afford an additional 9.3g (92% overall yield) of 6-fluoro-2- pyridinamine. A portion of the solid (5g, 0.044 mol) was dissolved in 1 ,2- dichloroethane (20 mL) and 1 ,3-dichloro-2-propanone (34.2 mL, 4.34 mol) was added in two portions. The reaction was stirred at 409 C over two days. The resulting solid was collected by filtration, dissolved in absolute ethanol (100 mL), and refluxed at 90Q C overnight. Solvent was evaporated and dichloromethane and saturated aqueous sodium bicarbonate was added to the residue. The aqueous layer was extracted two times with dichloromethane and once with a 3:1 chloroform: isopropanol mixture. Combined organics were dried over sodium sulfate and concentrated to a 3.61 g (62%) of 2-(chloromethyl)-5-fluoroimidazo[1 ,2-a]pyridine as a black oil which solidified upon standing. 1H NMR (400 MHz, DMSO-D6) δ 5.02 (s,2H), 7.29 (d, 1 H), 7.74 (d, 1 H), 7.88 (m, 1 H), 8.41 (s, 1 H); MS m/z 185 (M+1). EPO <DP n="47"/>B) 1 -[(5-fluoroimidazo[1 ,2-a]pyridin-2-yl)methyl]-1 ,2,3 ,4,4a,5,6,1 Ob-octahydro-1 ,10- phenanthroline: |
82.6% | Reference Example 58 Synthesis of 2-amino-6-fluoropyridine A solution of 30.0 g of 2,6-difluoropyridine in 150 mL (4.6 equivalents) was stirred in a sealed tube (inner pressure 12.1 kgcm-2) for 5 hours at 130 C. The reaction mixture was cooled to 0 C., which was left standing for two hours. Resulting crude crystals (plates) were collected by filtration with a glass filter, which were dried at 40 C. for 2 hours under reduced pressure (24.2 g, yield 82.6%). 1H-NMR (CDCl3, 300 MHz) δ: 4.33-4.74 (2H, br s), 6.20 (1H, m), 6.30 (1H, m), 7.48 (1H, m). Elemental analysis for C5H5H2F Calcd.: C, 53.57; H, 4.50; N, 24.97; F, 16.95 Found: C, 53.44; H, 4.45; N, 24.97; F, 17.25 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With CO2; lithium diisopropyl amide; In tetrahydrofuran; cyclohexane; | EXAMPLE 64 4-(3-Bromoanilino)-7-fluoropyrido[2,3-d]pyrimidine 2,6-Difluoronicotinic acid. 2,6-Difluoropyridine (7.89 mL, 0.087 mmol) is added dropwise under N2 at 78 C. to a stirred solution of lithium diisopropylamide (59.0 mL of a 1.5N solution in cyclohexane, 0.089 mmol) in THF (250 mL). After 2 h at 78 C., a stream of dry CO2 is passed through the solution and the mixture is diluted with water and washed with EtOAc. The aqueous portion is neutralized with 3N HCl, extracted with EtOAc and worked up to give 2,6-difluoronicotinic acid (13.4 g, 97%). 1 H NMR (DMSO) δ 8.59 (1H, dd, J=9.2, 8.2 Hz), 7.30 (1H, dd, J=8.2, 2.1 Hz), 4.03 (1H, brs). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With nitric acid; | a 2,6-Difluoro-3-nitropyridine To a mixture of concentrated sulphuric acid (600 mL) and fuming nitric acid (90%, 400 mL) in a ice-bath (internal temperature maintained at 5-10 C.) was added drop-wise 2,6-difluoropyridine (200 g, 1.74 mol). The resulting mixture was stirred overnight at room temperature. The mixture was poured slowly into 3 kg of ice and extracted with Et2O (2*2 L). The combined organic layers were washed with aqueous 1.5 N NaOH (2*1 L), then with aqueous saturated NaHCO3 (400 mL) or until pH is around 8-9. The organic layers were dried over MgSO4, filtrated and concentrated under reduced pressure until constant weight (to remove unreacted 2,6-difluoropyridine: 10-12%). The title compound was obtained as a yellow liquid (207.3 g, 74% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; | (1) Fifty (50) g of 2,6-difluoropyridine was dissolved in 200 ml of tetrahydrofuran, and into the solution 326 ml of 1.6M n-butyl lithium-tetrahydrofuran solution was added dropwise at -70 C., followed by an hour's stirring at the same temperature. To the reaction mixture 29 g of dry ice blocks were added little by little, followed by 30 minutes' stirring at the same temperature. Raising the temperature to about 5 C., 500 ml of ice water was added. The reaction mixture was washed twice with ethyl acetate, and the aqueous layer was adjusted to pH 3 with conc. hydrochloric acid. The aqueous layer was then extracted with chloroform. The extract was washed with saturated saline water, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. The crystalline precipitate was collected by filtration, and recrystallized from diethyl ether-n-hexane to provide 63 g of 2,6-difluoro-3-pyridinecarboxylic acid (m.p. 170-171 C.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Reference Example 30; (2,6-Difluoropyridin-3-yl)(phenyl)methanoneTo a solution of 2,6-difluoropyridine (1.0 g, manufactured by Tokyo Chemical Industry Co., Ltd.) in tetrahydrofuran (40 mL, manufactured by Kanto Chemical Co., Inc.), lithium diisopropylamide (23% solution in tetrahydrofuran/ethylbenzene/heptane, 5.79 mL, manufactured by Sigma-Aldrich Corp.) was added dropwise at -78 C., and the mixture was stirred for 30 minutes. Subsequently, N-methoxy-N-methylbenzamide (1.46 mL, manufactured by Sigma-Aldrich Corp.) was further added at the same temperature, and while the temperature was gradually raised to room temperature, the mixture was stirred overnight. A saturated aqueous solution of ammonium chloride (30 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (3×30 mL), washed with brine (30 mL), and dried (MgSO4). The solvent was then evaporated, to give 1.90 g of the title compound. LC-MS: HPLC retention time 1.63 minutes, m/z (M-F+OMe) 232, condition C-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trifluoromethanesulfonic acid anhydride; In dichloromethane; | Synthesis of 2,6-difluoro-3-nitropyridine Tetramethylammonium nitride (4.5 g) was suspended in dichloromethane (10 ml), and a solution of trifluoromethanesulfonic anhydride (5.56 ml) in dichloromethane (5 ml) was added dropwise at room temperature. After stirring at room temperature for 1.5 hours, a solution of 2,6-difluoropyridine (2 ml) in dichloromethane (5 ml) was added at room temperature, and the reaction solution was heated under reflux overnight. After leaving to cool, the reaction solution was poured into an ice-cooled saturated sodium bicarbonate solution. Dichloromethane was added and the organic layer was separated. The resulting organic layer was washed with brine and then dried over anhydrous sodium sulfate. The drying agent was separated by filtration and the organic layer was concentrated under reduced pressure to obtain the title compound (3.84 g). The property values of the compound are as follows. 1H-NMR (CDCl3) delta (ppm): 7.03-7.07 (m, 1H), 8.66-8.73 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Under N2, to a solution of 2,6-difluoropyridine (4.95 g, 43.0 mmol) in anhydrous THF (100 mL) cooled at- -78C was added LDA (2.0 M in heptane/THF/ethylbenzene, 23.0 mL, 46.0 mmol). After the mixture was stirred at -780C for 30 min 1-formylpiperidine (4.98 g, 44.0 mmol) was added. The mixture was stirred at -78C for 20 min, and at -78C aqueous HCl (3 N, 60 mL) and Et2O (50 mL) were added. The ether layer was collected and the aqueous layer was extracted with Et2O (3 X 100 mL). The combined extracts were dried over anhydrous Na2SO4. After filtration the solvent was removed, and the residue was purified by flash chromatography on silica gel (CH2Cl2/hexanes, 1:1 v/v) to afford 2,6-difluoro-pyridme-3- carbaldehyde as a pale yellow liquid (1.41 g, 60%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Under nitrogen protection,2,6-difluoropyridine (11.5 g, 0.1 mol),Boc2O (26.0 g, 0.12 mol) and tetrahydrofuran 130 mL,After stirring until completely dissolved,The ice salt bath drops to -15 C,Start the dropwise addition of a previously prepared 1M LDA tetrahydrofuran solution (0.13 mol).The temperature control during the whole dropping process does not exceed -10 C.After the addition is completed,Stir for 2-3 hours with heat.Then naturally rise to room temperature and stir the reaction overnight.There is almost no residue in the TLC test. The reaction solution was again lowered to 0 C.Add 15% hydrochloric acid aqueous solution to pH=1-2 (note that the acidity adjustment is not too strong,When not controlling the hydrolysis of acid,A small amount of 2-hydroxy-6-fluoro-pyridine-3-carboxylic acid was detected.Significantly exothermic during the addition process,Control temperature does not exceed 30 C,After the addition is completed, the temperature is raised to 35-40 C.Continue to stir the reaction for 1-2 hours.Detect if there is still a small amount remaining,It can be supplemented with 15% hydrochloric acid and then kept warm and stirred until the reaction is completed.After falling to room temperature,Then add saturated aqueous sodium carbonate solution,Adjust pH=4-5,Add ethyl acetate 70mL and extract twice.Washed with saturated saline,Dry over anhydrous sodium sulfate,After steaming the solvent,After beating with 88 mL of methyl tert-butyl ether and n-heptane (1:8 by volume),Obtained 13.5 g of 2,6-difluoropyridine-3-carboxylic acid as a pale yellow solid.Yield 85%,HPLC: 98.1%,The product is consistent with the standard sample in HPLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Under nitrogen protection,2,6-difluoropyridine (11.5 g, 0.1 mol) and tetrahydrofuran 120 mL,After stirring until completely dissolved,Dry ice/acetone system to -75 C,Start adding and pre-configuring1M LDA tetrahydrofuran solution (0.12 mol),The temperature control during the entire dropping process does not exceed -60 C.After the addition was completed, the mixture was stirred for 1.5 hours.Subsequently DBU-CO2 complex (0.11 mol)Dissolved in 65mL tetrahydrofuran solution,The temperature control does not exceed -60 C and drops into the reaction solution.Stir for 2 hours with heat.Naturally warm to room temperature and stir the reaction overnight.There is almost no residue in the TLC test.The reaction solution was again lowered to 0 C.A 15% aqueous hydrochloric acid solution was added dropwise to pH = 3-5.Significantly exothermic during the addition process,The control temperature does not exceed 20 C,After the addition is completed, the reaction is stirred for 1-2 hours.Add ethyl acetate 70mL and extract twice.Washed with saturated saline,Dry over anhydrous sodium sulfate,After steaming the solvent,After beating with 80 mL of methyl tert-butyl ether and n-heptane (1:8 by volume),A pale yellow solid of 12.9 g of 2,6-difluoropyridine-3-carboxylic acid was obtained in a yield of 81%. HPLC: 97.2%. |
Tags: 2,6-Difluoropyridine | Fluorinated Building Blocks | Pyridines | Heterocyclic Building Blocks | Organic Building Blocks | 1513-65-1
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P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
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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