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Bromonium-Mediated Electrochemical Synthesis of 3-Pyridinol from Biomass-Derived Furfurylamine
Yan, Kaili ; Kwon, Hyuna ; Huddleston, Morgan ; Jiang, De-en ; Sun, Yujie ;
Abstract: Electrocatalytic biomass valorization has attracted increasing interest over the years. Amongst many possible products from biomass upgrading, pyridine-containing chems. are rarely reported. Herein, we describe an electrochem. synthesis of 3-pyridniol from biomass-derived furfurylamine in 0.1 M H2SO4, taking advantage of the Br-/Br+ redox cycle and the strong acidic condition in driving the final dehydration step. Such an electrosynthesis approach was able to achieve a 97% yield of 3-pyridinol from the nearly complete conversion of furfurylamine. A number of control experiments aided by computational investigation were carried out to elucidate the key mechanistic steps of the ''one-pot'' conversion of furfurylamine to 3-pyridinol.
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CAS No. : | 109-00-2 |
Formula : | C5H5NO |
M.W : | 95.10 |
SMILES Code : | OC1=CC=CN=C1 |
MDL No. : | MFCD00006378 |
InChI Key : | GRFNBEZIAWKNCO-UHFFFAOYSA-N |
Pubchem ID : | 7971 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
92% | With iodine; sodium carbonate; In water; at 20℃; for 2h; | To a solution of 3-hydroxypyridine 4 (5.0 g, 52.57 mmol) in water (400 mL) was added Na2CO3 (11.6 g, 109.72 mmol) and iodine (13.3 g, 52.57 mmol). The reaction mixture was stirred for 2h at room temperature and a solution of HCl 1M was added until pH 4. The precipitate was filtered off, washed with cold water and dried to give 5 (10.7 g, 92%) as a white powder; mp (neat) 189-190C; Rf = 0.33 (CH2Cl2/EtOH 97/3); IR (KBr) νmax (cm-1): 2851, 2722, 2573, 2345, 15560, 1455, 1301, 1189, 1121, 794, 668; 1H NMR (400 MHz, DMSO-d6): δ 10.88 (s, 1H, OH), 7.87 (dd, 1H, J1=1.6 Hz, J2=4.4 Hz, H-6), 7.24 (dd, 1H, J1=4.4 Hz, J2=8 Hz, H-5), 7.18 (dd, 1H, J1=1.6 Hz, J2=8 Hz, H-4); 13C NMR (100 MHz, DMSO-d6): δ 154.0, 141.8, 124.3, 121.3, 110.9; HRMS calcd for C5H4INO [M+H]+ 221.9410 found 221.9416. |
90% | With iodine; sodium carbonate; In water; at 20℃; for 2h; | 3-hydroxypyridine (20.0 g, 0.21 mol) was added to a three-necked flaskAnd water (1600 mL); add sodium carbonate at room temperature(46.4 g, 0.44 mol) and elemental iodine (53.2 g, 0.21 mol),Stir at room temperature for 2 hours. Adjust pH = 4 with 1 N hydrochloric acidA lot of solids precipitated, filtered,Compound 1 (41.9 g, 0.19 mol, 90%) was dried. |
(a) 2-Iodo-3-hydroxypyridine This was prepared from 3-hydroxypyridine as described by Schickh, Binz & Schulz in Berichte [69] 2593 (1936). The product was recrystallized from methanol/water. For C5 H4 NOI, % theory (found): C: 27.1 (27.3); H: 1.8 (1.8); N: 6.3 (6.3); I: 57.5 (58.0). |
45 mg | With iodine; sodium carbonate; In water; at 0 - 20℃; for 2h; | To a stirring solution of 3-hydroxy pyridine (30 g, 315.78 mmol) in water (3000 mL) was added Na2CO3 (70 g, 663.15 mmol) followed by Iodine (80 g, 315.78 mmol) in portion wise at 0 C. The reaction mixture was allowed to stir at room temperature for 2 hrs. Reaction mass was acidified with iN HC1 up to pH -4 to get the solid which was filtered off, washed with chilled water followed by MTBE-Hexane to afford desired 3-hydroxy-2-iodopyridine (45 g) as off white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In dichloromethane; | EXAMPLE 1 Production of 3-benzyloxypyridine (2) To a suspension of 3-hydroxypyridine (24.7 g, 260 mmole) in distilled methylene chloride (260 ml) were added Adogen 464 (1.6 ml), 40% NaOH (130 ml), benzyl chloride (32 ml, 278 mmole), followed by stirring for 3 days at room temperature. The organic layer was separated from the reaction solution, and the aqueous layer was admixed with water and extracted with methylene chloride. The resulting extract was combined with the methylene chloride layer separated previously, and the combined solution was washed with saturated saline, dried over K2 CO3 and freed of the solvent by distillation. The residue was purified on a column of silica gel (7734, n-hexane:ethyl acetate=20:1 to 5:1). Yield of 8.6 g or 17.9%. | |
With sodium hydroxide;Adogen 464; In dichloromethane; water; at 20℃; | Step 15.1 : 3-Benzyloxy-pyridine; 9.5 g (10 mMol) 3-Hydroxy-pyridine and 9.45 ml (10 mMol) benzylchloride are dissolved in 50 ml CH2CI2 at rt. 0.5 g Adogen 464 (Aldrich 63393-96-4) are added followed by dropwise addition of 50 ml of aq. NaOH solution (40 %wt). The resulting yellow solution is stirred overnight, leading to formation of a white precipitate. The insolubles are filtered off and the filtrated is diluted with CH2CI2 and H2O. The phases are separated and the aq. phase is repeatedly extracted with CH2CI2. Combined organic extracts are dried, concentrated and the residual crude product is purified by flash chromatography (SiO2, CH2CI2/Me0H 95:5) to give the title compound as a yellow oil: MS: [M+1]+ = 186; 1H MNR (CDCI3): δ ppm 8.42 (s, 1 H), 8.26 (s, 1 H), 7.55-7.38 (m, 5H), 7.30-7.19 (m, 2H), 5.17 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.9% | To 629 mg (2.4 mmol) of PPh3 in 13 mL of dry THF at -20°C was added 378 muL (2.4 mmol) of DEAD dropwise. The solution was allowed to stir 10 min. at -20°C. After 10 min, a solution containing 220 muL (2.0 mmol) of <strong>[13220-33-2]1-methyl-3-hydroxypyrrolidine</strong> and 2 mL of dry THE was added dropwise. The solution was again allowed to stir 10 min at -20°C. After 10 min, to the solution was added 190 mg (2.0 mmol) of 3-hydroxypyridine at once. The solution was allowed to stir at room temperature overnight. Next day, solvent was removed under reduced pressure. The crude product was purified by flash chromatography (9 : 1, CHCl3 : MeOH) to obtain 260 mg (72.9 percent) of a clear oil:1H NMR (300 MHz, CDCl3) delta 8.26 (1H, d, J = 2.6 Hz), 8.20 (1H, d, J = 4.2 Hz), 7.22 - 7.13 (2H, m), 4.85 (1H, m), 2.89 - 2.76 (3H, m), 2.48 -1.95 (3H, m), 2.40 (3H, s); Mass spectrum (ESI) m/z 179.6 (M+H+). | |
260 mg (72.9%) | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; | EXAMPLE 7 3-(1-Methyl-3-pyrrolidinyloxy)-pyridine To 629 mg (2.4 mmol) of PPh3 in 13 mL of dry THF at -20° C. was added 378 muL (2.4 mmol) of DEAD dropwise. The solution was allowed to stir 10 min. at -20° C. After 10 min, a solution containing 220 muL (2.0 mmol) of <strong>[13220-33-2]1-methyl-3-hydroxypyrrolidine</strong> and 2 mL of dry THF was added dropwise. The solution was again allowed to stir 10 min at -20° C. After 10 min, to the solution was added 190 mg (2.0 mmol) of 3-hydroxypyridine at once. The solution was allowed to stir at room temperature overnight. Next day, solvent was removed under reduced pressure. The crude product was purified by flash chromatography (9:1, CHCl3:MeOH) to obtain 260 mg (72.9percent) of a clear oil: 1H NMR (300 MHz, CDCl3) delta 8.26 (1H, d, J=2.6 Hz), 8.20 (1H, d, J=4.2 Hz), 7.22-7.13 (2H, m), 4.85 (1H, m), 2.89-2.76 (3H, m), 2.48-1.95 (3H, m), 2.40 (3H, s); Mass spectrum (ESI) m/z 179.6 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 6.0h; | To a solution of 3-hydroxypyridine (3.25 g) in dimethylformamide (75 ml), 6.75 g of potassium carbonate and 5.0 g of l,3-difluoro-5-nitrobenzene were added, and the reaction solution was stirred at 100C for 6 hours. The reaction solution was cooled, thereafter diluted with a saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The combined organic layers were washed with water and a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resultant residue was purified by silica gel chromatography to yield the title compound as a yellow oil. ' H-NMR(CDCl3 )delta:7.05(lH,dt,J=8.6,2.4Hz),7.39-7.45(2H,m),7.62-7.64(lH,m),7.70(lH,dt,J=8.2,2.2H z),8.49(lH,d,J=2.2Hz),8.55(lH,dd,J=4.4,2.2Hz). ESI-MS Found:m/z 235.1[M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With sodium hydride; In DMF (N,N-dimethyl-formamide); at 0 - 20℃; | 60% NaH (4.42 g, 111 mmol) was added to a solution of Compound A (10.0 g, 105 mmol) in DMF (100 ml) at 0C, subsequently benzyl bromide (13.7 ml, 115 mmol) was added to the mixture. Then, the mixture was stirred at room temperature overnight. The reaction mixture was poured into ice-water, and extracted with diethyl ether. The extract was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate=97:3-50:50) to give Compound B (16.3 g, 84%) as a liquid. MS: 186 [M+H]+, APCI (MeOH) |
59% | With tetrabutylammomium bromide; potassium hydroxide; In tetrahydrofuran; for 12h;Reflux; | General procedure: Five grams (52.6 mmol) 3-hydroxypyridine, 5.9 g (110 mmol) pulverized potassium hydroxideand 0.85 g (2.6 mmol) nBu4NBr were dissolved in 150 mL of dried THF. After addition of 84 mmol ofthe respective alkyl halogenide the mixture was stirred for 12 h under reflux. The reaction was finishedwith the addition of 200 mL water and extraction with each 100 mL of hydrochloric acid (10%) fortwo times. The unified water phases were alkalined with a 10 M sodium hydroxide solution and thenextracted with each 75 mL of chloroform for three times. After removal of the solvent of the unifiedorganic layers in vacuum, the raw product was purified using column chromatography technique oversilica gel and an eluent mixture of cyclohexane and ethyl acetate in a relation of 1:1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 2,3,5-trimethyl-pyridine; hexane; mineral oil; | PREPARATION 6 3-(3,5-Dibromophenoxy)pyridine Sodium hydride (3.24 g of a 60% dispersion in mineral oil) was added portionwise to a stirred mixture of 3-hydroxypyridine (15.4 g), 1,3,5-tribromobenzene (76.4 g), cuprous oxide (11.6 g) and collidine (400 ml). When evolution of hydrogen had ceased, the mixture was heated at 200 for 8 hours and then cooled. The cool mixture was diluted with ethyl acetate and water, basified with aqueous ammonia (SG 0.880) and then filtered. The filtered residue was washed with ethyl acetate, then the washings and organic phase of the filtrate combined, washed with saturated brine and dried (MgSO4). The ethyl acetate was evaporated under vacuum, the collidine removed by distillation under vacuum and the residue chromatographed on silica gel using ether:hexane (1:4) as eluent. The earlier fractions gave, after evaporation under vacuum, recovered tribromobenzene (42.5 g). The later fractions were evaporated under vacuum to afford the title compound as an oil (18.55 g); δ (CDCl3): 7.07(2H,s), 7.22-7.26(2H,m), 7.42 (1H,s), 8.42(1H,s), 8.47(1H,d). Found: C,40.49; H,2.17; N,4.19. C11 H7 Br2 NO requires C,40.16; H,2.14; N,4.26%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | With potassium carbonate; In acetone; at 20℃; | K2CO3 (113 mg, 0.82 mmol) was added to a solution of 2-bromo-l-(2,4,6-trimethyl- phenyl)-ethanone (100 mg, 0.41 mmol) and 3-hydroxypyridine (39 mg, 0.41 mmol) in acetone (5 mL) at room temperature. The reaction was stirred overnight at room temperature then was quenched with of water. The extraction was conducted with EtOAc (x2) then the organic phase was washed with brine and dried over MgSO4. The crude residue was the purified by flash chromatography (hexane/EtOAc 0-40% gradient) to give the expected compound (17.3 mg, 17%) as brown oil. TLC single spot at R/ 0.9 (hexane/EtOAc 7:3); 1H NMR (270 MHz, CDCl3): £2.24 (s, 6H), 2.28 (s, 3H), 4.90 (s, 2H), 6.86 (s, 2H), 7.21 (t, J = 2.7 Hz, 2H), 8.25 (t, J = 3.0 Hz, IH), 8.31 (s br, IH); LC/MS (APCI) m/z 256 (M++H); HPLC tr = 1.85 min (98.8%) in 10% water-acetonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 80℃; for 3h; | General procedure: To a stirred solution of 35 (0.300g, 1.30mmol), appropriate hydroxypyridine (0.247g, 2.60mmol) and PPh3 (0.681g, 2.60mmol) in anhydrous THF (15mL) was added DIAD 95% (0.54mL, 2.60mmol) at 80C. After 3h, the mixture was concentrated under reduced pressure and EtOAc (100mL) was added. The organic layer was extracted with cold 0.1M aqueous HCl (2×40mL). 1 M aqueous NaOH (60mL) was added to the aqueous layer and the resulting mixture was extracted with EtOAc (2×100mL). The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by flash silica gel column chromatography eluting with Hexanes/EtOAc (7:3). 4.10.1 1,1-Dimethylethyl (S)-2,2-dimethyl-4-[[(3-pyridyl)oxy]methyl]-3-oxazolidinecarboxylate (15) Yellow oil. 53% yield: [alpha]D25+58 [alpha]D25+58 (c 3.46, CH2Cl2); IR v 3058, 2979, 2936, 2880, 1689, 1575, 1477, 1427, 1385, 1376, 1365cm-1; 1H NMR (200MHz, CDCl3) delta (ppm): 8.29-8.18 (m, 2H, Ar), 7.25-7.13 (m, 2H, Ar), 4.23-3.87 (m, 5H, CHN, CH2O, CH2OAr), 1.58, 1.53, 1.46 (s, 15H, CH3, C(CH3)3); 13C NMR (50MHz, CDCl3) delta (ppm) major rotamer: 154.57 (Ar), 152.21 (C=O), 142.07, 138.32, 123.71, 120.69 (Ar), 93.49 (C), 80.58 (C(CH3)3), 66.17, 65.00 (CH2O, CH2OAr), 55.79 (CHN), 28.29 (C(CH3)3), 27.41, 24.12 (CH3). HRMS (m/z): [MH+] calcd for C16H25N2O4, 309.1809; found, 309.1818. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydrogen sulphate; potassium carbonate; triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; | 7a. (S)-3-((2-Azetidinylmethyl)oxy)pyridine dihydrochloride An ice-cooled solution of 1-butyloxycarbonyl-2-(S)-azetidinemethanol (2.8 g, 15.0 mmol, Step 7c below) in THF (40 mL) was stirred under a nitrogen atmosphere. To this was added DEAD (3.54 mL, 22.46 mmol) followed by triphenylphosphine (4.78 g, 22.5 mmol) and the mixture was stirred 10 minutes. 3-Hydroxypyridine (2.14 g, 22.5 mmol) was then added to the reaction with additional tetrahydrofuran (40 mL). After 18 h, additional 3-hydroxypyridine (0.10 g, 1.05 mmol) was added and the reaction stirred 24 hours longer. When all starting azetidine alcohol was consumed, the reaction mixture was concentrated in vacuo. The crude mixture was then acidified (pH<2) with a 10% solution of potassium hydrogen sulfate (80 mL), and washed with ethyl acetate (3*75 mL). The aqueous portion was then basified with a saturated solution of potassium carbonate (pH=10) and products extracted with ethyl acetate (4*75 mL). These extracts were dried (MgSO4), filtered and concentrated in vacuo to a red-brown oil (1.84 g, 50% yield). Purification by flash silica gel chromatography Rf=0.19, (ethyl acetate:hexane=2:1) afforded the coupled product as a light yellow oil in 25% yield; MS (CI/NH3) m/z 265 (M+H)+, 282 (M+NH4)+; 1 H NMR (CDCl3) δ: 8.36-8.35 (dd, J=3.7 Hz, J=0.7 Hz, 1 H), 8.24-8.22 (dd, J=4.0 Hz, J=1.5 Hz, 1 H), 7.25-7.22 (m, 2H), 4.56-4.48 (m, 1 H), 4.36-4.31 (dd, J=10 Hz, J=4.9 Hz, 1 H), 4.17-4.12 (dd, J=10 Hz, J=2.9 Hz, 1 H), 3.92-3.87 (dd, J=8.2 Hz, J=6.8 Hz, 2H), 2.42-2.25 (m, 2H), 1.42 (s, 9H). To an ice-cooled solution of the compound from above (286 mg, 1.08 mmol) in absolute ethanol (4 mL), was added a hydrogen chloride saturated ethanol solution (4 mL), under nitrogen. The reaction mixture was stirred 18 hours while gradually warming to room temperature. The reaction mixture was then concentrated in vacuo, the product dissolved in absolute ethanol and triturated with diethyl ether. Two recrystallizations from ethanol and diethyl ether yielded pure title compound as a white powder (174 mg, 87 mmol, 81% yield): mp 135-137 C.; [α]D -5.0 (c 0.4, MeOH); MS (CI/NH3) m/z 165 (M+H)+, 182 (M+NH4)+. 1 NMR (D2 O, 300 MHz) δ: 8.60-8.59 (d, J=2.9 Hz, 1 H), 8.48-8.46 (d, J=5.8 Hz, 1 H), 8.25-8.21 (ddd, J=9.0 Hz, J=2.6 Hz, J=1.1 Hz, 1 H), 5.05-4.97 (m, 1 H), 4.59-4.57 (d, J=4.0 Hz, 2H), 4.22-4.05 (m, 2H), 2.77-2.67 (dd, J=16.9 Hz, J=8.45 Hz, 2H). Anal. calcd. for C9 H12 N2 O.2.7 HCl.0.2 H2 O: C, 40.60; H, 5.71; N, 10.52. Found: C, 40.75; H, 5.76: N, 10.51. |
Tags: 3-Hydroxypyridine | Pyridines | Alcohols | Organic Building Blocks | Heterocyclic Building Blocks | 109-00-2
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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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