Structure of 373-88-6
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Fluorinated Ethylamines as Electrospray-Compatible Neutral pH Buffers for Native Mass Spectrometry
Davis, Bradley T. V. ; Velyvis, Algirdas ; Vahidi, Siavash ;
Abstract: Native electrospray ionization mass spectrometry (ESI-MS) has emerged as a potent tool for examining the native-like structures of macromol. complexes. Despite its utility, the predominant "buffer" used, ammonium acetate (AmAc) with pKa values of 4.75 for acetic acid and 9.25 for ammonium, provides very little buffering capacity within the physiol. pH range of 7.0-7.4. ESI-induced redox reactions alter the pH of the liquid within the ESI capillary. This can result in protein unfolding or weakening of pH-sensitive interactions. Consequently, the discovery of volatile, ESI-compatible buffers, capable of effectively maintaining pH within a physiol. range, is of high importance. Here we demonstrate that 2,2-difluoroethylamine (DFEA) and 2,2,2-trifluoroethylamine (TFEA) offer buffering capacity at physiol. pH where AmAc falls short, with pKa values of 7.2 and 5.5 for the conjugate acids of DFEA for TFEA, resp. Native ESI-MS experiments on model proteins cytochrome c and myoglobin electrosprayed with DFEA and TFEA demonstrated the preservation of noncovalent protein-ligand complexes in the gas phase. Protein stability assays and collision-induced unfolding experiments further showed that neither DFEA nor TFEA destabilized model proteins in solution or in the gas phase. Lastly, we demonstrate that multisubunit protein complexes such as alc. dehydrogenase and Con A can be studied in the presence of DFEA or TFEA using native ESI-MS. Our findings establish DFEA and TFEA as new ESI-compatible neutral pH buffers that promise to bolster the use of native ESI-MS for the anal. of macromol. complexes, particularly those sensitive to pH fluctuations.
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CAS No. : | 373-88-6 |
Formula : | C2H5ClF3N |
M.W : | 135.52 |
SMILES Code : | FC(F)(F)CN.[H]Cl |
MDL No. : | MFCD00012875 |
InChI Key : | ZTUJDPKOHPKRMO-UHFFFAOYSA-N |
Pubchem ID : | 9772 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319 |
Precautionary Statements: | P261-P264-P280-P337+P313-P302+P352+P312-P304+P340+P312 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 21.59 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.04 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.57 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.96 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.86 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.08 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.27 |
Solubility | 7.29 mg/ml ; 0.0538 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.18 |
Solubility | 9.02 mg/ml ; 0.0666 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.73 |
Solubility | 25.2 mg/ml ; 0.186 mol/l |
Class? Solubility class: Log S scale |
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) |
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 |
-6.39 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 |
3.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.0 |
* 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 |
---|---|---|
100% | Stage #1: With tert-butyl methyl ether; sodium hydroxide In water at 20℃; for 0.5 h; Stage #2: at 5 - 10℃; for 1 h; |
To a 500 ml four-necked flask, 30.4 g (759.3 mmol) of sodium hydroxide and 50 g of water were added, dissolved at room temperature, and then cooled to 5 ° C. A solution prepared by dissolving 50 g (370.4 mmol) of 2,2,2-trifluoroethylamine hydrochloride in 60 g of water was added dropwise thereto at 5 ° C. After 85 g of tert-butyl methyl ether was added and stirred for 30 minutes, a solution of 43.9 g (388.9 mmol) of chloroacetyl chloride dissolved in 15 g of tert-butyl methyl ether was added dropwise while keeping at 5 ° C. The reaction solution was heated to 10 ° C. and stirred for 1 hour. After disappearance of 2,2,2-trifluoroethylamine was confirmed by gas chromatography, the temperature was raised to room temperature and liquid separation was carried out. The aqueous layer was extracted with 100 g of tert-butyl methyl ether, the organic layers were combined, the solvent was distilled off under reduced pressure to adjust the liquid volume, and 2-chloro-N- (2,2,2-trifluoroethyl) acetamide Of a tert-butyl methyl ether solution was obtained. As a result of the internal standardization by high performance liquid chromatography, the yield was 65 g, the yield was 100percent, and the concentration was 25.1 wtpercent. The melting point of 2-chloro-N- (2,2,2-trifluoroethyl) acetamide taken out by dropping the obtained solution in heptane and crystallizing it was 53.8 ° C. (DSC). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; triethylamine; In dichloromethane; | c. 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic Acid-(2,2,2-trifluoro-ethyl)-amide 23 g (0.063 mol) of 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid chloride are added dropwise to a solution of 9.35 g (0.069 mol) of 2,2,2-trifluoroethylamine-hydrochloride and 26 ml (0.188 mol) of triethylamine in 550 ml of dichloromethane at 0 C. under nitrogen and stirred for 2 hours at ambient temperature. The reaction mixture is extracted twice each with water, 1N hydrochloric acid and sodium hydrogen carbonate solution. The organic phase is dried over sodium sulphate and the solvent is distilled off. The product is purified by column chromatography on silica gel (eluant: cyclohexane/ethyl acetate=8:1). Yield: 15.8 g (58.6% of theory), Melting point: 172 C. | |
With triethylamine; In dichloromethane; | EXAMPLE III 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid-(2,2,2-trifluoro-ethyl)-amide 23 g (0.063 mol) of 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid chloride are added dropwise to a solution of 9.35 g (0.069 mol) of 2,2,2-trifluoroethylamine-hydrochloride and 26 ml (0.188 mol) of triethylamine in 550 ml of dichloromethane at 0 C. under nitrogen and stirred for 2 hours at ambient temperature. The reaction mixture is extracted twice with water, 1N hydrochloric acid and sodium hydrogen carbonate solution. The organic phase is dried over sodium sulphate and the solvent is distilled off. The product is purified by column chromatography on silica gel (eluant: cyclohexane/ethyl acetate=8:1). Yield: 15.8 g (58.6% of theory), melting point: 172 C. | |
With triethylamine; In dichloromethane; | c. 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid-(2,2,2-trifluoroethyl)-amide 23 g (0.063 mol) of 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid chloride are added dropwise at 0 C. under nitrogen to a solution of 9.35 g (0.069 mol) of 2,2,2-trifluoroethylamine-hydrochloride and 26 ml (0.188 mol) of triethylamine in 550 ml of dichloromethane and stirred for 2 hours at ambient temperature. The reaction mixture is extracted twice with water, 1N hydrochloric acid and sodium hydrogen carbonate solution. The organic phase is dried over sodium sulphate and the solvent is distilled off. Purification is by column chromatography on silica gel (eluant: cyclohexane/ethyl acetate=8:1). Yield: 15.8 g (58.6% of theoretical), Melting point: 172 C. |
With triethylamine; In dichloromethane; at 0℃; for 1h;Inert atmosphere; | To a solution of above obtained acid (60 g, 173 mmol) and DIVIF (100 1iL) inCH2C12 (600 mL) under argon at 00 C. was added oxalyl chloride (104 mL, 2.OM inCH2C12, 208 mmol) drop wise. The reaction was stined at 0C. for 10 mm, then warmed to RT and stined for 1.5 h. The reaction was concentrated to give the crude acid chloride as yellow oil. To a suspension of 2,2,2-trifluoroethylamine hydrochloride (25.9 g, 191 mmol) in CH2C12 (500 mL) at 0C. under argon was added triethylamine (73 mL, 521 mmol) followed by drop wise addition of a solution of the crude acid chloride in CH2C12(15 mL). The reaction was stined at 0 C. for 1 h, diluted with CH2C12 (500 mL), and washed with water (2x300 mL), iN HC1 (2x300 mL) to give 80 g of an oil whichwas purified by flash chromatography on silica gel (2.5 kg). The crude product was loaded in a mixture of CH2C12 and hexane, and eluted with a step gradient of 10% EtOAc/hexane (4L) to 15% EtOAc/hexane (2L) to 20% EtOAc/hexane (4L). Pure fractions were combined and evaporated to give 9-(4-bromobutyl)-N-(2,2,2- trifluoroethyl-9H-fluorene-9-carboxamide of formula II as a white solid.Yield: 52.5 gm.Chromatographic purity (by HPLC): E 90%.Dimer impurity A: 12.11%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50 mg (12.6%) | With triethylamine; trichlorophosphate; In water; acetonitrile; | EXAMPLE 55 2-Allylamino-4-(2,2,2-trifluoroethylamino)-6-nitroquinazoline To 250 mg (1.21 mmol) of <strong>[32618-85-2]6-nitroquinazoline-2,4(1H,3H)-dione</strong> were added 5.00 ml (53.64 mmol) of phosphorus oxychloride and 0.18 ml (1.21 mmol) of diisopropylformamide, and the resulting mixture was subjected to heating under reflux for 24 hours. After phosphorus oxychloride was removed in vacuo, the mixture was dissolved in 5 ml of acetonitrile, followed by addition of 328 mg (2.42 mmol) of 2,2,2-trifluoroethylamine hydrochloride and 1.69 ml (12.10 mmol) of triethylamine under ice cooling and stirring under ice cooling for 30 minutes. To the reaction solution was added water, followed by extraction with ethyl acetate, washing with brine and drying over anhydrous sodium sulfate. After the solvent was distilled off, 1.50 ml (20.00 mmol) of allylamine was added thereto, followed by stirring overnight, adding water to the reaction solution, extraction with ethyl acetate, washing with brine and drying over anhydrous sodium sulfate. After the solvent was distilled off, the residue was purified by a silica gel column to give 50 mg (12.6%) of the title compound. NMR (delta, CDCl3, 55 C.): 3.99-4.02 (2H, m), 4.34-4.43 (2H, m), 5.04-5.20 (2H, m), 5.88-5.98 (1H, m), 7.33 (1H, d, J=9 Hz), 7.51 (1H, br), 8.25 (1H, dd, J=9 Hz, 3 Hz), 8.93 (1H, br), 9.15 (1H, d, J=3 Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.1% | In a thermometer,In a three-necked flask of a dropping funnel,(25.0 g, 73 mmol), methylene chloride (250 ml), oxalyl chloride (11.0 g, 87 mol) and DMF (5 drops) under nitrogen atmosphere at room temperature for 2 h and the solvent was evaporated under reduced pressure , The residue was dissolved in dichloromethane (50 ml)A solution of trifluoroethylamine hydrochloride (10.9 g, 80 mmol)And triethylamine (31 ml, 220 mmol) in dichloromethane (100 ml). The organic phase was washed with water, 1N HCl solution, saturated aqueous NaHCO3 solution and saturated brine (200 ml x 3 times each), dried over anhydrous Na2SO4, and evaporated to remove the solvent. The residue was purified by silica gel column chromatography (eluent: To give a light yellow oil which was recrystallized from anhydrous ethanol (200 ml) at -5 C and the solid was collected to give the title compound as an intermediate (4) (23.7 g, 76.1%) as a white solid, | |
73% | To a solution of 9-(4-bromobutyl)-9H-fluorene-9-carboxylic acid (200 gm, 0.579 moles) in dichloromethane (4 L) was charged N-methyl morpholine (87.88 gm, 0.87 moles). The reaction mass was cooled to about 0-5C under nitrogen atmosphere and isobutylchloroformate (102.68 gm, 0.75 moles) was added slowly at about 0-5C. The reaction mass was stirred for about 15 min at same temperature and a suspension of 2,2,2-trifluoroethylamine hydrochloride (94.2 gm, 0.70 moles) and N-methyl morpholine (87.88 gm, 0.868 moles) in dichloromethane (1 L) was slowly added. The reaction mass was stirred for about 8-12 hrs at room temperature. After completion of the reaction, water was added to the reaction mass at about 25-30C and the layers were separated. The organic layer was washed with dilute hydrochloric acid followed by water. The organic layer was distilled off under vacuum at about 35-40C to afford a residue. Water was added to the solution of residue in methanol and the obtained mass was stirred. The precipitated solid was filtered and dried under vacuum at about 50-55C for about 12 hrs to afford 180 gm of 9-(4-bromobutyl)-N-(2,2,2-trifluroethyl)-9H-fluorene-9-carboxamide as pale yellow solid (Yield 73 %, HPLC purity 95.40 %). | |
71% | To a solution of Part A(1) acid (60 g, 173 mmol) and DMF (100 µL) in CH2Cl2 (600 mL) under argon at 0C was added oxalyl chloride (104 mL, 2.0M in CH2Cl2, 208 mmol) dropwise. The reaction was stirred at 0C for 10 min, then warmed to room temperature and stirred for 1.5 h. The reaction was concentrated in vacuo to give the crude acid chloride as a yellow oil. To a suspension of 2,2,2-trifluoroethylamine hydrochloride (25.9 g, 191 mmol) in CH2Cl2 (500 mL) at 0C under argon was added triethylamine (73 mL, 521 mmol) followed by dropwise addition of a solution of the crude acid chloride in CH2Cl2 (15 mL). The reaction was stirred at 0C for 1 h, diluted with CH2Cl2 (500 mL), and washed with water (2 x 300 mL), 1N HCl (2 x 300 mL), saturated NaHCO3 (2 x 300 mL), and brine (2 x 300 mL), then dried over MgSO4. Evaporation gave 80 g of a oil which was purified by flash chromatography on silica gel (2.5 kg). The crude product was loaded in a mixture of CH2Cl2 and hexane, and eluted with a step gradient of 10% EtOAc/hexane (4L) to 15% EtOAc/hexane (2L) to 20% EtOAc/hexane (4L). Pure fractions were combined and evaporated to give title compound (52.5 g, 71%) as a white solid (mp 88-92C). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine; In dichloromethane; at 20℃; for 5h;Inert atmosphere; | General procedure: To a solution of a 2-chloro-4,5-dihydroimidazolium chloride in CH2Cl2 was added Et3N followed by a primary amine at r.t. and the mixture was stirred at r.t. After the addition of ice-water and then 20percent aq NaOH solution, the mixture was extracted with toluene. The combined organic solution extracts were washed with H2O and rine to give a guanidine that was purified by column chromatography(silica gel or NH-silica gel) if necessary. An alkyl bromide was added to a solution of the guanidine in MeCN at r.t. and then the mixture was stirred at r.t. After evaporation of the solvent the residue was isolated either as the bromide by successively washing with hexane and Et2O or after purified by column chromatography (silica gel) if necessary as the hexafluorophosphate by treatment with aq NH4PF6 solution at r.t. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
155 g | A mixture of 9H-fluorene-9-carboxylic acid compound of formula-2a (100 gm), 1,4-dibromobutane (308 gm) and toluene (1000 ml) was stirred for 15 mm at 25-30C undernitrogen atmosphere. Cooled the reaction mixture to 5-10C, sodium tert.butoxide (100.5 gm) was slowly added to it and stirred the reaction mixture for 3 hrs at the same temperature. Water was added to the reaction mixture at 25-30C and stirred for 15 mm at the same temperature. Filtered the reaction mixture through hyflow bed and washed the hyflow bed with water. Both the organic and aqueous layers were separated and washed the aqueouslayer with toluene. Acidified the aqueous layer using aqueous hydrochloric acid solution at25-30C aiid stirred the reaction mixture for 20 mm at the same temperature. Dichioromethane was added to the reaction mixture at 25-30C and stirred for 15 mm at the same temperature. Both the organic and aqueous layers were separated and washed the organic layer with aqueous citric acid solution. Distilled off the solvent completely from theorganic layer. Dichioromethane (500 ml) was added to the reaction mixture at 25-30C and stirred for 15 mm at the same temperature. N,N-dimethylformamide (6.9 gm) followed by oxalyl chloride (66.4 gm) were slowly added to the reaction mixture at 25-30C and stirred for 2 hrs at the same temperature. Distilled off the solvent completely from the reaction mixture under nitrogen atmosphere and co-distilled with dichloromethane under reducedpressure. Dichloromethane (500 ml) was added to the obtained compound at 25-30C and stirred for .15 mm at the same temperature. The obtained compound was slowly added to a pre-cooled mixture of water (500 ml), 2,2,2-trifluoroethylamine hydrochloride (64.4 gm) and sodium carbonate (75.6 gm) at 5-10C and stirred the reaction mixture for 45 mm at the same temperature. Both the organic and aqueous layers were separated and washed the organiclayer with aqueous hydrochloric acid solution followed by with aqueous sodium bicarbonate solution and then finally washed with water. Distilled off the solvent completely from the organic layer and then co-distilled with n-heptane under reduced pressure. n-Heptane (100 ml) and isopropanol (5 ml) were added to the reaction mixture at 25-30C. Heated the reaction mixture to 55-60C and stirred for 1 hr at the same temperature. Cooled the reaction ttiture to 25-30C and stirred for 1 hr at the same temperature. Filtered the precipitatedsolid, washed with n-heptäne and then dried the material to provide the title compound. The PXRD pattern of the obtained compound is shown in figure-5.Yield: 155.0 gm; M.R: 95-102C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 120℃; | General procedure: A mixture of the corresponding nitrobenzene compound (1.0 equiv.), a suitable amine (1.1 equiv.), and /V,/V-diisopropylethylamine (1.2 equiv.) was stirred in 2-propanol at 120 C for 12 - 72 h. Thereafter, the mixture was poured into NaHC03 and extracted with DCMx3. The combined organics were dried (using MgS04), filtered, concentrated, and purified by silica gel chromatography |
Tags: 373-88-6 synthesis path| 373-88-6 SDS| 373-88-6 COA| 373-88-6 purity| 373-88-6 application| 373-88-6 NMR| 373-88-6 COA| 373-88-6 structure
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P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
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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