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[ CAS No. 373-88-6 ] {[proInfo.proName]}

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Chemical Structure| 373-88-6

Chemical Structure| 373-88-6

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Product Citations

Product Citations

Fluorinated Ethylamines as Electrospray-Compatible Neutral pH Buffers for Native Mass Spectrometry

Davis, Bradley T. V. ; Velyvis, Algirdas ; Vahidi, Siavash Anal. Chem.,2023,95(48):17525-17532. DOI: 10.1021/acs.analchem.3c02640 PubMed ID: 37997939

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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.

Purchased from AmBeed: 373-88-6 ; 79667-91-7

Product Details of [ 373-88-6 ]

CAS No. :	373-88-6	MDL No. :	MFCD00012875
Formula :	C₂H₅ClF₃N	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZTUJDPKOHPKRMO-UHFFFAOYSA-N
M.W :	135.52	Pubchem ID :	9772
Synonyms :

Calculated chemistry of [ 373-88-6 ] Expand+

Physicochemical Properties

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 :	26.02 ?2

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.39 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.04
Log Po/w (WLOGP) :	2.57
Log Po/w (MLOGP) :	0.96
Log Po/w (SILICOS-IT) :	0.86
Consensus Log Po/w :	1.08

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	3.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.27
Solubility :	7.29 mg/ml ; 0.0538 mol/l
Class :	Very soluble
Log S (Ali) :	-1.18
Solubility :	9.02 mg/ml ; 0.0666 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.73
Solubility :	25.2 mg/ml ; 0.186 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.0

Safety of [ 373-88-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P264-P280-P337+P313-P302+P352+P312-P304+P340+P312	UN#:	N/A
Hazard Statements:	H302+H312+H332-H315-H319	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 373-88-6 ]

* 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.

Upstream synthesis route of [ 373-88-6 ]
Downstream synthetic route of [ 373-88-6 ]

[ 373-88-6 ] Synthesis Path-Upstream 1~1

1
[ 373-88-6 ]
[ 79-04-9 ]
[ 170655-44-4 ]

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).

Reference： [1] Patent: JP5652628, 2015, B2, . Location in patent: Paragraph 0057
[2] Inorganic Chemistry, 2018, vol. 57, # 17, p. 11252 - 11263
[3] Chemical Communications, 2016, vol. 52, # 96, p. 13885 - 13888

[ 373-88-6 ] Synthesis Path-Downstream 1~10

1
[ 373-88-6 ]
[ 331767-53-4 ]
[ 182438-98-8 ]

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%.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 5067 - 5070
[2]Journal of Medicinal Chemistry,2001,vol. 44,p. 851 - 856
[3]Patent: US2003/166637,2003,A1
[4]Patent: US2003/114442,2003,A1
[5]Patent: US6818644,2004,B1
[6]Patent: WO2016/71849,2016,A1 .Location in patent: Page/Page column 15; 16

2
[ 869-07-8 ]
[ 32618-85-2 ]
[ 373-88-6 ]
[ 107-11-9 ]
[ 221042-30-4 ]

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)

Reference： [1]Patent: US2001/6969,2001,A1

3
[ 373-88-6 ]
[ 182438-97-7 ]
[ 182438-98-8 ]

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).

Reference： [1]Patent: CN106146385,2016,A .Location in patent: Paragraph 0037; 0038
[2]Patent: WO2016/55934,2016,A1 .Location in patent: Paragraph 0124; 0133
[3]Patent: EP904262,2004,B1 .Location in patent: Page 145

4
[ 128742-76-7 ]
[ 373-88-6 ]
[ 1574373-77-5 ]

Reference： [1]Organic Letters,2014,vol. 16,p. 1606 - 1609

5
[ 373-88-6 ]
[ 37091-73-9 ]
C₇H₁₂F₃N₃ [ No CAS ]

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.

Reference： [1]Synthesis,2014,vol. 46,p. 2201 - 2219

6
[ 53308-95-5 ]
[ 373-88-6 ]
C₁₂H₂₁F₃N₂O₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 7195 - 7216

7
[ 373-88-6 ]
[ 51293-47-1 ]
C₁₁H₁₉F₃N₂O₄ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 7195 - 7216

8
[ 373-88-6 ]
[ 35344-95-7 ]
[ 1424799-64-3 ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 7950 - 7962

9
[ 110-52-1 ]
[ 1989-33-9 ]
[ 373-88-6 ]
[ 182438-98-8 ]

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-hept?ne 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.

Reference： [1]Patent: WO2017/98522,2017,A1 .Location in patent: Page/Page column 18; 19; 24; 25

10
[ 19064-24-5 ]
[ 373-88-6 ]
3-fluoro-2-nitro-N-(2,2,2-trifluoroethyl)aniline [ No CAS ]

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

Reference： [1]Patent: WO2019/166639,2019,A1 .Location in patent: Page/Page column 87; 92; 194

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P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
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

Ghs Hazard Statements

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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