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CAS No. : | 2142-06-5 | MDL No. : | MFCD00516834 |
Formula : | C11H11NO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | IONNJVQITCVNHK-UHFFFAOYSA-N |
M.W : | 189.21 | Pubchem ID : | 95241 |
Synonyms : |
|
Num. heavy atoms : | 14 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.27 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 55.73 |
TPSA : | 37.38 Ų |
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) : | -7.0 cm/s |
Log Po/w (iLOGP) : | 1.89 |
Log Po/w (XLOGP3) : | 0.64 |
Log Po/w (WLOGP) : | 0.8 |
Log Po/w (MLOGP) : | 1.62 |
Log Po/w (SILICOS-IT) : | 2.0 |
Consensus Log Po/w : | 1.39 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.6 |
Solubility : | 4.74 mg/ml ; 0.025 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.0 |
Solubility : | 18.9 mg/ml ; 0.0999 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -3.03 |
Solubility : | 0.178 mg/ml ; 0.00094 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.0 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
57% | With sodium tetrahydroborate; In methanol; dichloromethane; at 0℃; for 2h; | To a 0 C solution of <strong>[2142-06-5]N-benzylsuccinimide</strong> 3 (3 g, 16 mmol) in CH2Cl2-MeOH (80 mL, 1 : 3), NaBH4 (1.5 g, 40 mmol) was added portionwise over a period of 2 h with stirring. Then water (50 mL) was added and the volatiles were removed in vacuo. The precipitate formed was collected by filtration, washed with water and air-dried. The filtrate was extracted with dichloromethane, dried with MgSO4, and the solvent was removed in vacuo to give the addition crop of the target product. The products were combined and recrystallized from benzene. White powder, m.p.110-111 C (cf. Ref. 26: m.p. 105-106 C), yield 1.73 g (57%). 1H NMR (CDCl3), delta: 1.84-1.97 (m, 1 H, C(O)CH2CHaHb); 2.16-2.39 (m, 2 H, C(O)CH2); 2.50-2.70 (m, 1 H,C(O)CH2CHaHb); 4.27 (d, 1 H, OH, J = 7.8 Hz); 4.17 (d, 1 H, NCHaHbPh, J = 14.8 Hz); 4.85 (d, 1 H, NCHaHbPh, J = 14.8 Hz); 5.03-5.12 (m, 1 H, CH); 7.22-7.38 (m, 5 H, Ph). 13C NMR (CDCl3), delta: 28.10, 29.00, 43.42, 82.47, 127.67, 128.35, 128.76, 136.55, 174.98. |
50% | With sodium tetrahydroborate; In tetrahydrofuran; ethanol; at 0℃; for 3h; | N-benzylsuccinamidal: Powered sodium borohydride (0.5 g, 10.75 mmol) was added portionwise to a stirred solution of <strong>[2142-06-5]N-benzylsuccinimide</strong> (1.0 g, 5 mmol) in 1:1 tetrahydrofuran-ethanol (15 mL) at 0 C. After 3 h, the reaction was quenched by the addition of 10% aqueous hydrochloric acid (2.5 mL) and the mixture was diluted with water, extracted with ethyl acetate, and dried with Na2SO4 and concentrated. A solid was obtained which had m.p. 104-106 C after crystallization from ethyl acetate (0.65 g, 50%). 1H NMR (300 MHz, CDCl3) ppm 1.74-2.72 (m, 4 H), 4.15 (d, J = 15.1 Hz, 1 H), 4.84 (d, J = 15.1 Hz, 1 H), 5.07 (dd, J = 2.1 Hz, 4.2 Hz, 1 H), 7.30 (s, 5 H). Anal. Calcd for C11H13NO2: C 69.09 H 6.85 N 7.32; found: C 69.12, H 6.78, N 7.17. IR (KBr, cm-1) 3355, 1685 (C=O). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With ammonium peroxodisulfate; In 1,4-dioxane; dimethyl sulfoxide; at 100℃; for 7h; | General procedure: A solution of amine (1 equiv) and anhydride (1.1 equiv) in 1,4-dioxane was stirred at room temperature (or 100 C if necessary) in a two neck round bottom flask equipped with a water condenser. As soon as all the amine converts to the corresponding amic acid (monitored by TLC), ammonium persulfate [(NH4)2S2O8] (2 equiv) and DMSO (2 equiv) were added and the reaction mixture was heated to 100 C. Heating was continued at the same temperature until completion (3-10 h) of the reaction. After completion, the reaction mixture was filtered through a cotton plug and dioxane was removed under vacuo. The residue was dissolved in ethyl acetate and washed with dilute HCl, saturated aqueous NaHCO3 and brine. The organic layer was dried over anhydrous Na2SO4 and evaporated under vacuo to furnish the corresponding imides in good to excellent yields with more than 98% purity (GC, NMR). |
92% | With sodium acetate; acetic anhydride; for 2h;Reflux; | To N-benzylsuccinic acid monoamide, calcined sodium acetate (1.02 g, 12.15 mmol) and acetic anhydride (50 mL) were added and the mixture was refluxed for 2 h. Removal of the solvent in vacuo and recrystallization of the residue from diethyl ether afforded N-benzylsuccinimide (3), white crystals, m.p. 96-98 C (cf. Ref. 26: m.p. 102-103 C), yield 8.7 g (92%). 1H NMR (CDCl3), delta: 2.68 (s, 4 H, 2 CH2); 4.65 (s, 2 H, PhCH2); 7.28-7.39 (m, 5 H, Ph). |
With sodium acetate; acetic anhydride; for 2h;Reflux; | General procedure: The synthesis of maleimides 1-47 was performed by mixing an equimolar amount of the appropriate maleic anhydrides 68-72 in 5 mL of CHCl3 and anilines 73, 78-90, amines 91-94 or phenylalkylamines 74-77 (5 mmol) dissolved in 1 mL of CHCl3 and stirred during 1 h. The solid (maleamic acid) which precipitated out of the reaction mixture was filtered off. The whole amount of maleamic acid was dissolved in 5 mL of acetic anhydride and 100 mg of sodium acetate was added. The mixture was heated for 2 h under reflux. The reaction was cooled and quenched with water; then, the aqueous solution was extracted with Et2O, dried with Na2SO4, filtered, and the solvent was evaporated. The product was purified by silica gel column chromatography using a mixture of hexane and ethyl acetate (9:1) as eluent. Compounds 1-10, 16-26, 31-34, 36, 38-42 and 43-47 were previously reported.[3], [8], [21], [22], [23], [24], [25], [26], [27] and [28] |
With sodium acetate; acetic anhydride; for 0.5h; | General procedure: In a 100 mL three-necked flask provided with a stirrer, a reflux condenser, and adropping funnel were placed 2.0 g (20 mmol) of succinic anhydride and 25 mL of diethylether. The succinic anhydride dissolved upon stirring, at which point a solution of 1equiv. (20 mmol) of the corresponding amine in 5 mL of diethyl ether was run throughthe dropping funnel. The resulting thick suspension was stirred at room temperature for 1h and was then cooled in an ice bath. The N-substituted succinamic acid was recoveredby filtration and dried. The residue was then added to a flask containing a solution ofanhydrous sodium acetate (0.65 g, 8 mmol) in acetic anhydride (6.7 mL) and stirred overa steam bath for 30 min. The reaction mixture was then cooled to room temperature in acold water bath and was then poured into 100 mL of an ice-water mixture. Theprecipitated product was recovered by filtration, washed three times with 30 mL portionsof ice-cold water, and dried. The crude N-substituted succinimide was recrystallized fromethanol/water to afford the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With bis(1,5-cyclooctadiene)diiridium(I) dichloride; hydrogen; sodium t-butanolate; In isopropyl alcohol; at 40℃; under 30003.0 Torr; for 12h;Autoclave; Sealed tube; | Add 38 mg of <strong>[2142-06-5]1-benzylpyrroline-2,5-dione</strong> (0.2 mmol), 2.2 mg of sodium tert-butoxide, and 2 ml of isopropanol under nitrogen protection. Add 5 mul of 0.001 M catalyst (S / C = 40,000), then the reaction flask was transferred to an autoclave, the reaction kettle was tightened, 4 MPa of hydrogen was charged, and the reaction was carried out at 40 C for 12 hours. After the reaction was completed, the mixture was naturally cooled to room temperature, and the hydrogen was carefully released. The celite was filtered, and the organic solvent was removed from the filtrate to obtain 38 mg of a yellow oil with a yield of 99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9.5 g N-Benzylsuccinimide is added to 120 ml THF and the mixture is then cooled to -78 C. A solution of 4-methylbiphenylmagnesium chloride in THF (1.3 eq) is then added. The subsequent mixture is then stirred for 2 h at -78 0C. The mixture is then warmed to 10 0C and 100 ml saturated ammonium chloride solution is added. The phases are separated and the aqueous phase is extracted with toluene. The combined organic phases are washed with water then brine and then concentrated in vacuo. The crude material is crystallized from toluene to give 1-Benzyl-5-biphenyl-4-ylmethyl-5-hydroxy- pyrrolidin-2-one. 1H NMR (DMSO): 1.72 (1 H), 1.91 (1 H), 2.27 (2H)1 2.72 (1 H), 2.97 (2H), 4.40 (1 H), 4.55 (1 H), 7.21-7.66 (14H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | Intermediate 54; 5-Cvclopropyl-5-hvdroxy-1-(phenylmethyl)-2-pyrrolidinone; To <strong>[2142-06-5]1-(phenylmethyl)-2,5-pyrrolidinedione</strong> (1 g, 5.29 mmol) in THF (50 ml.) at -78 0C was added cyclopropylmagnesium bromide (42.3 ml_, 21.1 mmol) dropwise. The reaction mixture was allowed to warm to 0 0C and stirred for an additional 2 hours. The reaction was quenched with a saturated aqueous solution of ammonium chloride and transferred to a separatory funnel. EtOAc was added, and the organic phase was separated. The aqueous layer was further extracted with EtOAc, and the combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated. Flash chromatography onSiO2 (gradient: 100% hexanes to 80% EtOAc/hexanes) afforded the title compound (400 mg, 33%) as a yellow solid. LC-MS (ES) m/z = 232 [M+H]+. | |
33% | To <strong>[2142-06-5]1-(phenylmethyl)-2,5-pyrrolidinedione</strong> (1 g, 5.29 mmol) in THF (50 ml.) at -78 0C was added cyclopropylmagnesium bromide (42.3 ml_, 21.1 mmol) dropwise. The reaction mixture was allowed to warm to 0 0C and stirred for an additional 2 hours. The reaction was quenched with a saturated aqueous solution of ammonium chloride and transferred to a separatory funnel. EtOAc was added, and the organic phase was separated. The aqueous layer was further extracted with EtOAc, and the combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated. Flash chromatography on SiO2 (gradient: 100% hexanes to 80% EtOAc/hexanes) afforded the title compound (400 mg, 33%) as a yellow solid. LC-MS (ES) m/z = 232 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sodium hydride;dihydridotetrakis(triphenylphosphine)ruthenium; acetonitrile; 1,3-di(propan-2-yl)-1H-imidazol-3-ium bromide; In toluene; for 24h;Inert atmosphere; Reflux;Product distribution / selectivity; | [0013] Figure 5 illustrates the synthesis of succinimides from 1,4-butanediol. Common reaction conditions: 3a (0.5 mmol, 1.0 equiv), amine (1.1 equiv), lc (5 mol %), 1,3- diisopropylimidazolium bromide (2) (5 mol %), NaH (20 mol %), CH3CN (5 mol %), toluene (0.5 mL), reflux, 24 h. [b]: Isolated yields, average of at least two runs.[0057] A reaction of 1 ,4-butanediol (3a) and benzylamine (4a) to afford N-benzyl- succinimide (5a) was chosen to screen the catalytic conditions (Fig. 4). The investigation was started based on the reported Ru catalytic systems for the amide synthesis by others (Naota, T, & Murahashi, SI, Synlett (1991) 693; Watson, AJA, et al., Org. Lett. (2009) 11, 2667; Nordstram, LU, et al., J. Am. Chem. Soc. (2008) 130, 17672; Gunanathan, C, et al., Science (2007) 317, 790) and the present inventors (Ghosh, SC, et al., Adv. Synth. Catal. (2009) 351, 2643; Zhang, Y, et al., Organometallics (2010) 29, 1374; Muthaiah, S, et al., J. Org. Chem. (2010) 75, 3002). [Ru(benzene)Cl2]2 (la) (Ghosh, SCS, et al., Adv. Synth. Catal. (2009) 351, 2643) and [Ru(p-cymene)Cl2]2 (lb) (ibid.) showed limited activity even with the help of an N- heterocyclic carbene (NHC) precursor, 1,3-diisopropylimidazolium bromide (2), under basic conditions (entries 1 and 2). Usage of the reported [Ru(p-cymene)Cl2]2 with diphenylphosphi- nobutane (dppb) ligand did not exhibit any activity for the imide synthesis (entry 3) (Watson et al., 2009, supra). Then, the inventors noticed an early example of the use of RuH2(PPh3)4 (lc) for the synthesis of cyclic lactam from alpha,omega-aminoalcohols by Naota and Murahashi (Synlett (1991) 693). Although their original condition using a hydrogen acceptor afforded no amount of 5a (entry 4), RuH2(PPh3)4 showed good activity (70%) with the help of the NHC precursor 2 (entry 5). Further optimization has been attempted by applying different NHC precursors, however, the reported condition using 2 has been identified most active, see Muthaiah et al. (J. Org. Chem. (2010) 75, 3002) for more detailed screening conditions. The NHC promoted RuH2(PPh3)4 based catalyst was recently reported to be active on the synthesis of amides from either alcohols or aldehydes with amines (ibid.). Other catalytic systems based on Id (Nordstram et al., 2008, supra) and le (Gunanathan et al., 2007, supra) exhibited less activity on the cyclic imide synthesis (entries 6 and 7).;General Procedure for the Synthesis of Cyclic Imides[0065] RuH2(PPh3)4 (28 mg, 0.025 mmol), 1,3-diisopropylimidazolium bromide (5.8 mg, 0.025 mmol), NaH (2.4 mg, 0.10 mmol) and acetonitrile (1.2 mu-, 0.025 mmol) were placed in an oven dried Schlenk tube inside the glove box; toluene (0.5 mL) was added to the mixture over there. The Schlenk tube was taken out and heated to reflux in an oil bath under an argon atmosphere. The flask was removed from the oil bath after 20 min and a diol (0.50 mmol) and an amine (0.55 mmol) were added. The reaction mixture was heated to reflux under a flow of argon to facilitate removal of hydrogen for 24 h before being cooled to room temperature. All the volatiles were removed under vacuum. Purification of the crude product was performed by flash chromatography. Characterization of Cyclic Imides 5a-5w[0066] All reported cyclic imides were identified by spectral comparison with literature data or with analogous literature data. l-(Phenylmethyl)-2,5-pyrroUdinedione (5a) [Reddy, PY, et al., J. Org. Chem. (1997) 62, 2652][0067] White solid, isolated yield: 70%. lH NMR (CDCI3, 300MHz): delta = 7.23-7.38 (m, 5H), 4.63 (s, 2H), 2.68 (s, 4H);13C NMR (CDCI3, 100 MHz): delta = 176.88, 135.82, 128.91, 128.64, 127.97, 42.39, 28.21. |
69% | With C21H35BrMnN2O2P; potassium hydride; In toluene; for 40h;Reflux; Inert atmosphere; | Complex 6B was found to be active in the catalytic dehydrogenative coupling of diols and amines to form cyclic amides. The reaction between 1,4-butanediol and amine afford N- substituted succinimide derivatives in excellent yields (Table 23). When a toluene solution containing 1.2 mmol of 1,4-butanediol, 1 mmol of 2-phenethylamine, 5% of complex 6B and 10% of KH was refluxed under an argon atmosphere, quantitative conversion of the amine was observed by NMR and GC-MS after 40 hours, to give l-(phenylethyl)succinimide (characterized by NMR and GC-MS) in 88% isolated yield after column purification (Table 23, Entry 1). Excellent relativities where observed with benzyl amines. Reaction of 1,4-butanediol with benzylamine in toluene in analogous conditions resulted in 99 conversion, and the corresponding succinimide was isolated in 69% yield (Table 23, Entry 2). Refluxing of 1,4-butanediol and 4-fluorobenzylamine and toluene in the presence of the mixture 6B/KH, provided the succinimide in 72% yield (Table 23, Entry 3). More electron rich benzyl amines favored the cyclization reactions than electron-poor ones (Table 23, entries 3 and 5). In the case of alkyl amines, the imide was obtained in lower yield under analogous conditions (Table 23, Entries 6-8). The catalyst was sensitive to steric hindrance, thus reaction of 1 ,4-butanediol and cyclohexylamine rendered N-cyclohexylsuccinimide in 46% yield. It is noted that gamma-Butyrolactone was observed, especially with low yielding substrates, along with other unidentified by-products, presumably from possible inter- and intra-molecular amidation and esterifications reactions |
Tags: 2142-06-5 synthesis path| 2142-06-5 SDS| 2142-06-5 COA| 2142-06-5 purity| 2142-06-5 application| 2142-06-5 NMR| 2142-06-5 COA| 2142-06-5 structure
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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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