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Structure of 352-11-4
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 352-11-4 |
Formula : | C7H6ClF |
M.W : | 144.57 |
SMILES Code : | FC1=CC=C(CCl)C=C1 |
MDL No. : | MFCD00000913 |
InChI Key : | IZXWCDITFDNEBY-UHFFFAOYSA-N |
Pubchem ID : | 9602 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H227-H302-H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3265 |
Packing Group: | Ⅱ |
* 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 |
---|---|---|
85% | With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 100℃; for 3h; | General procedure: Aldehydes2 and 3 were synthesized by alkylation of 4-hydroxybenzaldehydeaccording to modified procedure[11]. A mixture of 30 mL of DMF, 6.1 g (50 mmol) of4-hydroxybenzaldehyde, 48 mmol of benzyl or 4-fluorobenzyl chloride, 6.9 g (50 mmol) of potassium carbonate , and 83 mg (0.5 mmol) of potassium iodide was heated for 3 h at 100C on an oil bath. The mixture was cooled to room temperature and dilutedwith 200 mL of water, and the precipitate was filtered off, washed several times with water, and dried. |
84% | With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 12h; | A mixture of 10 mmol of p-hydroxy benzaldehyde(1) and 10 mmol of 1-(chloromethyl)-4-fluorobenzene (2) in DMF was stirred at 120 C for 12 hours using K2CO3 as a catalyst. The reaction mixture was poured in crushed ice.The crude product 4-((4-fluorobenzyl)oxy) benzaldehyde(3) was isolated and recrystallized from absolute hot ethanol.Yield: 84% M.P: 99 C. |
With potassium carbonate; In acetonitrile; at 80℃; | General procedure: A mixture of 4-hydroxybenzaldehyde (1.0 g, 8.2 mmol), K2CO3 (2.2 g, 8.2 mmol), and alkyl bromide or benzyl chloride derivatives (8.2 mmol) were placed into a round bottomed flask containing 30 mL of acetonitrile. The mixture was then stirred and heated at 80 C for 12-24 h. After the completion of the reaction, the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (30 mL), washed with water (10 mL 3), and then dried over anhydrous MgSO4 to give compounds 6a-w. |
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; | General procedure: Toa solution consisting of 4-hydroxybenzaldehyde (10 mmol) or 6-hydroxy-2-naphthaldehyde (10 mmol) and K2CO3(10 mmol) in dry DMF (20 mL), the corresponding substituted benzyl chloride (10mmol) was added to the stirred solution 8-12 h at 60 oC. After the reaction is completed, the mixture waspoured into ice water, after which it solidifies. The resulting precipitate wasfiltered, washed with ethanol and recrystallized with ethanol to obtain crudeproducts which purifiedby column chromatography (dichloromethane : petroleum ether = 10 : 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water; | Step B: 2-chloro 1-(4 fluorobenzyl) benzimidazole 11 g 2-chlorobenzimidazole are dissolved in 74 ml water and 17.35 ml 30% sodium hydroxide. The mixture is heated to 82 C. and to this they are slowly added 23.76 g 4-fluorobenzyl chloride within 5 hours. When the reaction is achieved, the solution is cooled to 20 C. and extracted with methylene chloride. The compound is recrystallized from ethyl acetate. | |
With potassium iodide; sodium carbonate; In chloroform; N,N-dimethyl-formamide; | EXAMPLE 8 A mixture of 60 parts of 2-chloro-1H-benzimidazole, 58 parts of 1-(chloromethyl)-4-fluorobenzene, 42.5 parts of sodium carbonate, 0.1 parts of potassium iodide and 135 parts of N,N-dimethylformamide was stirred and heated overnight at 70 C. The reaction mixture was poured into water. The precipitated product was filtered off and dissolved in trichloromethane. The solution was dried, filtered and evaporated. The residue was crystallized from 2,2'-oxybispropane, yielding 62.5 parts of 2-chloro-1-(4-fluorophenylmethyl)-1H-benzimidazole (61). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With sodium hydrogencarbonate; In ethanol; for 1.5h;Heating / reflux; | k) 9-(4-Fiuorobenzvi)-3-oxa-7.9-diazabicvc)or3.3.11nonane-7-carboxviic acid tert-butyl ester; 3-Oxa-7,9-diazabicyclo[3.3.1]nonane-7-carboxylic acid tert-butyl ester (97 mg; 0.4 mmol) in EtOH (4 ml) is combined with 4-fluorbenzylchlorid (0.051 ml; 0.4 mmol) and NaHC03 (179 mg; 2.1 mmol) and refluxed for 1.5 h. The reaction mixture is evaporated, taken up in TBME, filtered and purifed via chromatography (TBME/hexanes 2/8 to 3/7) to yield the title compound as colorless crystals (95 mg; 67 %) 1 H-NMR (400MHz; DMSO-d6), No. (ppm) : 1.40 (s, 2.50 (s, 3.28(d, 1 H); 3.42 (d, 1H) ; 3.68 (dd, 2H) ; 3.73-3.88 (m, 4H) ; 3.91 (s, 2H) ; 7.13 (t, 2H) ; 7.41 (dd, 2H). MS (m/z) ES+: 337.2 (MH+, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.4% | 6-Hydroxyl-l,3-dihydro-l-hydroxy-2,l-benzoxaborole (lmmol) was dissolved in DMF (1OmL) and cooled to 00C with ice bath. To this solution under nitrogen were added in sequence sodium hydride (160mg, 4mmol, 4.0eq) and 1- (chloromethyl)-4-fluorobenzene (0.485mL, 4mmol, 4.0eq). The reaction mixture was stirred for 2 hours then treated with IM HCl (10ml). After extraction with ethyl acetate, the organic layer was washed with water and saturated brine. After rotary evaporation, the residue was purified by column chromatography over silica gel to give the title compound (228.2mg, 88.4percent yield). 1H NMR (300 MHz, DMSO-d6): delta 9.13 (s, IH), 7.53-7.11 (m, 7H), 5.10 (s, 2H) and 4.91 (s, 2H) ppm. Mp 136-137°C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Example 7 - Alternative method for making (2-[(4-Fluorophenyl)methyl]thio}-4-oxo-4,5,6,7- tetrahydro-lHcyclopenta[d]pyrimidin-l-yl)acetic acid) (4-Oxo-2-thioxo-2,3,4,5,6,7-hexahydro-lH- cyclopenta [ /]pyrimidin-l-yl)acetic acid (20.0 g, 1.0 eq) was slurried in a mixture of water (112 mL) and isopropyl alcohol (20 mL). NaOH solution (50.9% aqueous, 13.82 g, 1.99 eq) was added followed by a water line wash (10 mL) resulting in a solution. Then Na2C03 (1.50 g, 0.16 eq) was charged and the solution was heated to 40+/-3 C. Thereafter 4-fluorobenzyl chloride (13.4 g, 1.05 eq) was added, followed by a line wash of isopropyl alcohol (12 mL) and the reaction mixture was stirred at 40+/-3 C until the reaction was deemed complete ( ~2.5 hours). The reaction mixture was cooled to 20+/-3 C and formic acid (2.4 g, 0.6 eq) was added resulting in crystallisation of the product within 30 minutes. A second charge of formic acid (6.9 g, 1.7 eq) was added over 1 hour and the slurry was stirred at 20+/-3 C for at least one hour. The slurry was filtered to isolate the product, which was washed twice with a mixture of water (32 mL) and isopropyl alcohol (8 mL), then with isopropyl alcohol (40 mL) and dried in vacuo at 50 C to yield the title compound as an off-white solid (28.6 g, 97%th). 1H NM R (d6 DMSO) delta 1.95 (2H, m), 2.57 (2H, t), 2.85 (2H, t), 4.4 (2H, s), 4.7 (2H, s), 7.15 (2H, dd), 7.45 (2H, dd), ~13.6 (1H, vbrs). | |
76% | With potassium carbonate; potassium hydroxide; In water; isopropyl alcohol; at 40℃; for 3h; | Compound 1 (0.3603 g, 1.6 mmol, 1 eq) was stirred in a mixture of water (2 mL) and isopropyl alcohol (360 muL). KOH aqueous solution (50% w/v, 500 muL, 1.9 eq) was added. K2CO3 (0.0332 g, 0.24 mmol, 0.15 eq) was added and the solution was heated to 40 C. Then 4-fluorobenzyl chloride (0.2197 g, 1.52 mmol, 0.95 eq) was added and the reaction was stirred at 40 C for 3 hours. The reaction was cooled to room temperature and formic acid (30 muL, 0.8 mmol, 0.5 eq) was added to crystallize the product. After 30 min, more formic acid (103 muL, 2.7 mmol, 1.7 eq) was slowly added and the reaction was stirred for at least an hour until crystallization was complete. The product was isolated through filtration and washed twice with a 4:1 mixture of water and isopropyl alcohol (1 mL), then with isopropyl alcohol (1 mL). The product was stirred in ether for 2 hours to remove remaining organic impurities and filtered again. Product was dried in vacuo at 50 C to yield 2 (0.4082g, 1.22 mmol, 76%). |
60% | With potassium carbonate; potassium hydroxide; In Isopropyl acetate; water; at 40℃; for 3h; | Compound 1 (1 eq, 1.62 mmol) was stirred in a mixture of water (3 mL) and isopropyl alcohol (820 muL). KOH aqueous solution (50% w/v, 1.9 eq, 3.08 mmol) was added followed by K2CO3 (0.15 eq, 0.24 mmol) and the reaction was heated to 40 C under stirring. 4-fluorobenzyl chloride (0.95 eq, 1.52 mmol) was then added and the reaction was stirred at 40 C for 3 hours. The reaction was cooled to room temperature and formic acid (0.5 eq, 0.8 mmol) was added to crystallize the product. After 1h, more formic acid (1.7 eq, 2.7 mmol) was slowly added and the reaction was stirred for an hour until crystallization was complete. The product was collected through filtration and washed twice with a 4:1 (v:v) mixture of water and isopropyl alcohol (1 mL) followed by isopropyl alcohol (1 mL). The product was stirred in ether overnight and filtered again. Product was dried at 50 C to obtain the title compound as a colourless solid (300 mg, 60%). 1H NMR (DMSO-d6) delta: 12.54 (s, 1H), 7.47 (m, 2H), 7.11 (m, 2H), 4.65 (s, 2H), 4.45 (s, 2H), 2.82 (t, J = 7.3 Hz, 2H), 2.60 (t, J = 7.3 Hz, 2H), 1.99 (quint, J = 7.3 Hz, 2H). |
60% | With potassium carbonate; potassium hydroxide; In water; isopropyl alcohol; at 40℃; for 3h; | Compound 11' (1 eq, 1.62 mmol) was stirred in a mixture of water (3 mL) and isopropyl alcohol (820 mu). KOH aqueous solution (50% w/v, 1.9 eq, 3.08 mmol) was added followed by K2CO3 (0.15 eq, 0.24 mmol) and the reaction was heated to 40C under constant stirring. 4-fluorobenzyl chloride (0.95 eq, 1.52 mmol) was then added and the reaction was stirred at 40C for 3 hours. The reaction was cooled to room temperature and formic acid (0.5 eq, 0.8 mmol) was added to crystallize the product. After lh, more formic acid (1.7 eq, 2.7 mmol) was slowly added and the reaction was stirred for at least an hour until crystallization was complete. The product was collected through filtration and washed twice with a 4: 1 (v:v) mixture of water and isopropyl alcohol (1 mL) followed by isopropyl alcohol (1 mL). The product was stirred in ether overnight to remove remaining organic impurities and filtered again. Product was dried at 50C to afford the title compound as a colourless solid (300 mg, 60%). M.p. 183-185C 1H-NMR (CDCI3, 600 MHz) delta 12.54 (s, 1H), 7.45 (dd, J = 8.6, 5.6, 2H), 7.11 (t, J = 8.6, 2H), 4.63 (s, 2H), 4.43 (s, 2H), 2.82 (t, J = 7.3, 2H), 2.59 (t, J = 7.3, 2H), 1.97 (q, J = 1.3, 2H); 13C-NMR (CDCI3, 150 MHz) delta: 168.3, 165.7, 161.6 (d, JCF = 240 Hz), 156.7, 133.2 (d, JCF = 3 Hz), 131.3 (d, JCF = 7.5 Hz), 119.8, 115.3 (d, JCf = 21Hz), 50.1, 34.6, 31.4, 28.0, 20.2 ; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With NHC-Pd(II)-Im; lithium tert-butoxide; In toluene; at 130℃; for 3h;Inert atmosphere; Sealed tube; | Under N2 atmosphere, LiOtBu (1.0 mmol), benzoxazole 2a (0.6 mmol), NHC-Pd(II)-Im complex 1 (2.0 mol %), dry toluene (2.0 mL) and benzyl chloride 3a (0.5 mmol) were successively added into a sealed tube. The mixture was stirred vigorously at 130 C for 3 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the residue was purified by flash column chromatography on silica gel to afford pure product 4a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Compound 3 (5 mmol), NaH (15 mmol) was added to a 25 mL round bottom flask and 6 mL of anhydrous acetonitrile. After stirring at room temperature for 1 h, p-fluorobenzyl chloride (6.5 mmol) dissolved in anhydrous acetonitrile was slowly added dropwise to the reaction system at room temperature for 5 -7h, TLC The reaction was complete and the insoluble solids were removed by filtration. The filtrate was concentrated in vacuo and recrystallized from a petroleum ether: ethyl acetate = 4: 1 solvent system. The product was a yellow solid 4, yield 98.4% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22.75 g | With sodium ethanolate; In ethanol; for 36h;Heating; | Weighed 18.30g of <strong>[436-77-1]fangchinoline</strong>base,0.20 g of sodium ethoxide was dissolved in 360 mL of absolute ethanol in a 500 mL three-necked flask.Then add 13.60g of p-fluorobenzyl chloride, stir and heat to boiling,And the reaction was stirred for 36 hours.TLC was used to detect the total reaction of the <strong>[436-77-1]fangchinoline</strong>base, and the anhydrous ethanol was distilled off, and the temperature was lowered to room temperature.Add 150 mL of water and extract 3 times with chloroform (200 mL × 3), TLC tracking reactionSeparation and purification process with the product, the extract recovers chloroform,The solid was dried at 60 C for 4 h to give 22.75 g of product as pale yellow powder.The desired product has the melting point: 203.2-204.7 C, 13C NMR (CDCl3, 100 MHz) delta 163.55, 161.11,153.75, 151.39, 149.43, 148.78, 148.52, 147.13, 143.95, 137.41, 137.29, 136.98, 135.12,134.68, 133.61, 133.54, 133.35, 132.65, 132.55, 132.43, 130.15, 130.09, 130.01, 128.73,128.65, 128.43, 128.26, 128.10, 127.96, 127.83, 127.26, 127.11, 123.12, 122.82, 121.91,120.23, 116.14, 114.89, 114.68, 112.94, 111.59, 106.04, 73.62, 64.07, 61.51, 56.16,55.93, 55.83, 45.65, 44.77, 44.54, 44.29, 42.60, 42.41, 41.98, 39.05, 25.36, 22.23. TOF-HRMS: M/e (1005.9834), molecular formula: C58H57O6N2F3Cl2, that is, compound III3 in Table 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With potassium carbonate; In acetonitrile; at 25℃; for 10.0h; | General procedure: To a solution of <strong>[5294-61-1]N-(2,6-dimethylphenyl)-2-(piperazin-1-yl)acetamide</strong> 4 in acetonitrile, different substituted benzyl chlorides 7a-e (0.001 mol) were slowly added drop wise in presence of K2CO3 (0.003 mol). Reaction mixture was stirred for 10 h at 25oC and completion of reaction was checked by TLC. Reaction mixture was poured into ice-cold water and extracted with methylene dichloride. The organic layers was washed with brine solution, dried over anhydrous sodium sulphate and concentrated to get alkylated piperazine derivatives 8a-e in good yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17.85 g | With sodium ethanolate; In ethanol; at 78.5℃; for 36h; | Weighed 18.30g of <strong>[436-77-1]fangchinoline</strong>,2.10g of sodium ethoxide dissolved in 200mL of absolute ethanol in a 500mL three-necked flask, and thenAdd 5.80g of p-fluorobenzyl bromide, stir and heat 78.5 C, and stir the reaction for 36h. TLC test all <strong>[436-77-1]fangchinoline</strong> Should, dilute anhydrous ethanol, cool to room temperature, add 80mL of water, extract 3 times with chloroform (300mL × 3), TLC tracking reaction andThe product is separated and purified, the extract is recovered with chloroform, and the solid is dried at 60 C for 4 h to obtain a pale yellow powder.The product was 17.85 g. |
Tags: 352-11-4 synthesis path| 352-11-4 SDS| 352-11-4 COA| 352-11-4 purity| 352-11-4 application| 352-11-4 NMR| 352-11-4 COA| 352-11-4 structure
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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 |
Sorry,this product has been discontinued.
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