There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
Accessible (Haz class 3, 4, 5 or 8), Domestic | USD 100+ |
Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 57-41-0 | MDL No. : | MFCD00005264 |
Formula : | C15H12N2O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CXOFVDLJLONNDW-UHFFFAOYSA-N |
M.W : | 252.27 | Pubchem ID : | 1775 |
Synonyms : |
5,5-Diphenylhydantoin;NSC 8722;NCI-C55765;Lehydan;Hydantol;Diphenylhydantoin;Diphenylan;Diphenat;Diphedan;Dilabid;Dihycon;Di-Hydan
|
Chemical Name : | 5,5-Diphenylhydantoin |
Num. heavy atoms : | 19 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.07 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 77.5 |
TPSA : | 58.2 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.09 cm/s |
Log Po/w (iLOGP) : | 1.65 |
Log Po/w (XLOGP3) : | 2.47 |
Log Po/w (WLOGP) : | 0.9 |
Log Po/w (MLOGP) : | 1.61 |
Log Po/w (SILICOS-IT) : | 2.42 |
Consensus Log Po/w : | 1.81 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -3.3 |
Solubility : | 0.128 mg/ml ; 0.000506 mol/l |
Class : | Soluble |
Log S (Ali) : | -3.34 |
Solubility : | 0.116 mg/ml ; 0.000461 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -5.62 |
Solubility : | 0.000607 mg/ml ; 0.0000024 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 0.0 |
Synthetic accessibility : | 1.83 |
Signal Word: | Danger | Class: | 6.1 |
Precautionary Statements: | P201-P202-P260-P264-P270-P280-P301+P312+P330-P307+P311-P405-P501 | UN#: | 2811 |
Hazard Statements: | H302-H340-H351-H360-H370 | Packing Group: | Ⅱ |
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 |
---|---|---|
85% | With sodium hydroxide; sodium chloride In water at 5 - 30℃; for 1 h; | Example 2; Preparation of Phenytoin Sodium in Water with Sodium chloride (20percent w.r.t Phenvtoin); Phenytoin (2Og) was dissolved in 120 mL of DM water and Sodium hydroxide solution (3.56g dissolved in water 22.5mL) at 25-300C in a 250 mL four-necked RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (4g Dissolved in water 1OmL) was added to it. The reaction mass was cooled to 5-100C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum nitrogen atmosphere and washed the product with 2OmL of chilled water. The solid was dried at 50-600C under nitrogen atmosphere to obtain 18.5g of dry Phenytoin sodium. Yield : approx. 85percent w.r.t. Phenytoin; Example 3; Preparation of Phenvtoin Sodium in Water with Sodium Chloride (30percent w.r.t Phenvtoin); Phenytoin (25g) was dissolved in 150 mL of DM water and Sodium hydroxide solution (4.45g dissolved in water 25mL) at 25-300C in a 250 mL four-necked RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (7.5g Dissolved in water 22mL) was added to it. The reaction mass was cooled to 5-100C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum <n="6"/>nitrogen atmosphere and washed the product with 2OmL of chilled water. The solid was dried at 50-600C under nitrogen atmosphere to obtain 25.3g of dry Phenytoin sodium. Yield : approx. 93percent w.r.t. Phenytoin; Example 4; Preparation of Phenytoin Sodium in Water with Sodium Chloride (40percent w.r.t Phenvtoin); Phenytoin (25g) was dissolved in 150 mL of DM water and Sodium hydroxide solution (4.45g dissolved in water 25mL) at 25-300C in a 250 mL four-necked RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (1Og Dissolved in water 28mL) was added to it. The reaction mass was cooled to 5-100C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum nitrogen atmosphere and washed the product with 2OmL of chilled water. The solid was dried at 50-600C under nitrogen atmosphere to obtain 25.9g of dry Phenytoin sodium. Yield: approx. 95.3percent w.r.t. Phenytoin; Example 5; In-situ preparation of Phenytoin Sodium in Water with Sodium chloride (20percent w.r.t phenvtoin); Potassium hydroxide (152g) was dissolved in 96mL of DM water in a 3 L RBF. Methanol (48OmL) was charged at 25-300C and cooled to 0-50C. Urea (49.5g) and lOOg of Benzil was charged at 0-50C. The reaction mixture was refluxed for 60min and 144OmL of water was added to it and was cooled to 00C. 1Og of hyflo 1Og of activated carbon was added and stirred for 30-60min at 0-5° C. The reaction mixture was filtered through hyflo bed and washed with chilled 10OmL of water and collected into a 3 L RBF. The pH was adjusted to 6.0 - 7.0 with cone, hydrochloric acid at 30-45° C. The slurry was stirred for 30min, filtered and washed with 100OmL hot water to obtain 178. Ig wet Phenytoin having moisture contents 38.7percentw/w. The anhydrous weight was found to be 109.2g.Phenytoin (178g) was dissolved in 600 mL of DM water and Sodium hydroxide solution (16.7g dissolved in water 105mL) at 30-400C in a 2 L RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (2 Ig dissolved in <n="7"/>water 32mL) was added to it. The filtrate was cooled to 5-100C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum nitrogen atmosphere and washed with 10OmL of chilled water. The solid was dried at 50-600C under nitrogen atmosphere to obtain 102.6g of dry Phenytoin sodium. |
66.2% | With sodium hydroxide In water at 5 - 30℃; for 1 h; | Example 1; Preparation of Phenytoin Sodium in Water; Phenytoin (2Og) was dissolved in 120 mL of DM water and Sodium hydroxide solution (3.56g dissolved in water 22.5mL) at 25-300C in a 250 mL four-necked RBF. The reaction mixture was filtered and the clear filtrate was collected. The reaction mass was cooled to 5-100C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum nitrogen atmosphere and washed the product with 2OmL of chilled water. The solid was dried at 50-600C under nitrogen atmosphere to obtain 14.4g of dry Phenytoin sodium. Yield: approx. 66.2percent w.r.t. Phenytoin |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With potassium carbonate In N,N-dimethyl-formamide | |
With sodium hydroxide | ||
With sodium ethanolate Reflux; |
Stage #1: phenythoin With potassium <i>tert</i>-butylate In N,N-dimethyl-formamide at 20℃; for 0.05h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 0.0833333h; | General Procedure: Methylation of Phenytoin (1a) Using tBuOK (Table 1, run 8) General procedure: To a solution of phenytoin (1a, 100 mg, 0.40 mmol) in THF (2.0 mL), tBuOK (Aldrich, 1 M solution in THF, 0.80 mL, 0.80 mmol) was added at r.t. After 3 min, CH3I (30 µL, 0.48 mmol) in THF (0.1 mL) was added at r.t. and the mixture was stirred at r.t. for 5 min. One molar HCl (2 mL) was added and the whole was extracted with AcOEt (2×10, 1×5 mL). The combined organic layer was washed with brine (1×5 mL) and dried over Na2SO4. The solvent was evaporated in vacuo, and the crude product was purified by column chromatography (n-hexane-AcOEt 2 : 1) to give 4a as colorless solids (83 mg, 79%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With trichloroisocyanuric acid In acetonitrile at 20℃; for 0.5h; | |
31% | With sodium hypochlorite Ambient temperature; | |
25% | With sodium hypochlorite for 3h; |
4.7% | With hydrogenchloride; sodium hypochlorite for 4h; Ambient temperature; | |
With sodium hypochlorite |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sodium hydroxide In ethanol; water at 100℃; for 1h; | 2.5. General procedure for one-pot synthesis of phenytoin derivatives General procedure: To a mixture of 1,2-diketone (0.2 mmol), urea (0.26 mol), Fe3O4 (30mol%) and 50% ethanol (v/v, 0.5 mL), 20% NaOH aq. (0.15 mL) wasadded. The reaction mixture was heated to 80 °C in the presence of air.After completion of reaction, the catalyst was separated magnetically.The mixture was filtered, and the filtrate was acidized by 5% hydrochloricacid solution until solid completely precipitated. After filtration,the crude product was purified by preparative thin-layer chromatographywith dichloromethane-methanol (v/v=50:1). |
With potassium bromate; sodium hydroxide | ||
With sodium hydroxide; potassium chlorate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With potassium hydroxide In water; dimethyl sulfoxide for 0.5h; microwave irradiation; | |
1: 61.75% 2: 3.76% | With sodium hydroxide In water; dimethyl sulfoxide at 70℃; for 2h; | |
With potassium hydroxide |
With potassium hydroxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium hydroxide In ethanol; water monomer at 20℃; for 0.05h; Sonication; | |
98% | With chitosan decorated Fe3O4 magnetic nanoparticles In ethanol; water monomer at 60℃; for 0.133333h; Green chemistry; | |
98.2% | With dmap; potassium hydroxide In water monomer; butan-1-ol at 119℃; for 0.666667h; | 3 Condensation reaction:Add 10.5 g of dibenzoyl to a 500 mL three-neck round bottom flask.9g urea,10.64g potassium hydroxide,0.305 g of 4-dimethylaminopyridine,105 mL of n-butanol,125mL distilled water,Magnetically stirred and heated to 119 ° C for 40 min.The heating was stopped after the reaction was completed.The reaction solution was cooled to room temperature, poured into a 500 mL separatory funnel, 3 × 100 mL distilled waterExtracting 3 times, combining the aqueous phase and partially filtering the aqueous phase, filtering out the brown by-product, combining the filtrate and the organic phase, using HCl solutionAfter adjusting the pH to 5.5, the ice salt bath, white crystals are precipitated, and suction filtration is performed.The filter cake was dried in an oven at 108 ° C to a constant weight.Obtaining 12.37 g of phenytoin, the yield is 98.2%, and the liquid phase content is 99%; |
93% | With potassium hydroxide In water monomer; butan-1-ol at 100℃; for 2h; | |
93% | With PEG 600 In water monomer; butan-1-ol for 2h; Heating; | |
90.8% | With benzyl bromide modified CaO In ethanol at 40℃; for 15h; | |
80% | With sodium hydroxide In water monomer for 1h; Reflux; | |
75% | With sodium hydroxide In ethanol Heating; | |
73% | With MgAl calcined hydrotalcite In methanol at 64.84℃; for 24h; | |
73% | With potassium hydroxide for 1.5h; Milling; | |
70% | With sodium hydroxide at 20℃; for 0.5h; regioselective reaction; | |
65% | With potassium hydroxide In ethanol for 3h; Reflux; | 5,5-Diphenylimidazolidine-2,4-dione (phenytoin) (1) Potassium hydroxide 70% (8.1 mL), urea (2.30 g,0.04 mol) and benzil 4 (4.20 g, 0.02 mol) were addedto ethanol (45 mL) in a round-bottom flask. The doughformed was refluxed for 3 h and became clear by heating.Then cold distilled water was added (100 mL) and thediphenylacetylenediurein precipitate was discarded. Asolution of 50% sulfuric acid was added to the filtrate,with stirring, until acidic pH. The precipitate so formedwas filtered under vacuum and washed with cold distilledwater. The crystals were recrystallized from a solution ofhot distilled water (4.5 mL) and sodium hydroxide (1.88 g,0.05 mol) and treated with activated charcoal (0.3 g). Afterfiltration on Celite, a solution of 50% sulfuric acid wasadded to the filtrate until precipitation of the product as abeige colored solid, which was filtered and dried in oven at100 C, yielding a beige powder (3.28 g, 0.013 mol, 65%);mp 297-300 C; IR (KBr) ν / cm-1 3273, 3208, 1773, 1741,1718, 1494, 1449, 1401, 1235, 1015, 787, 641; 1H NMR(300 MHz, DMSO-d6) d 11.13 (s, 1H), 9.33 (s, 1H),7.31-7.44 (m, 10H); 13C NMR (75.46 MHz, DMSO-d6) d174.9, 156.1, 139.9, 128.6, 128.1, 126.7, 70.3. |
65% | With polymer supported zinc(II)-salen complex In ethanol; water monomer at 65℃; for 4h; Green chemistry; | General procedure for the synthesis of hydantoin and thiohydantoin derivatives (3a-j) catalyzed by (1f) General procedure: Slightly altering the process from the literature for preparation of hydantoin and thiohydantoin derivatives was achieved by refluxing a mixture of benzil (1 mmol, 210 mg), urea or thiourea derivative (1.5 mmol), in aqueous ethanol (H2O/EtOH, 7:3) in the presence of 10 mg catalyst at 65 °C for 4 h. The reaction progress was monitored by TLC (petroleum ether:ethyl acetate, 7:3 v/v). After the completion of the reaction, the heterogeneous catalyst was separated by filtration and the filtrate was acidified with concentrated HCl to precipitate the desired product. The resulting solids were recrystallized from aqueous ethanol to give pure products. (3a) 5,5-Diphenylimidazolidine-2,4-dione (Yield = 65%); 1H NMR (400 MHz, DMSO-d6) δ = 11.06 (s, 1H), 9.27 (s, 1H), 7.41-7.31(m, 10H). 13C NMR (100 MHz, DMSO-d6) 174.70, 155.86, 139.84, 128.39, 127.91, 126.48, 70.12. FT-IR (KBr) in cm-1: NH (3265, 3194), C=O (1770, 1710). GC-MS m/z: calcd. for C15H12N2O2: 252.0899, found 252.1824. |
44% | With sodium hydroxide In water monomer for 2h; Reflux; | |
41% | With sodium hydroxide In ethanol; water monomer for 3h; Inert atmosphere; Reflux; | |
With potassium hydroxide In dimethyl sulfoxide microwave irradiation; | ||
In dimethyl sulfoxide for 0.583333h; Microwave irradiation; Alkaline conditions; | ||
Stage #1: dibenzoyl; urea With methanol; potassium hydroxide In water monomer at 0℃; for 1h; Heating / reflux; Stage #2: With hydrogenchloride In methanol; water monomer at 30 - 45℃; for 0.5h; | 5 Example 5; In-situ preparation of Phenytoin Sodium in Water with Sodium chloride (20% w.r.t phenvtoin); Potassium hydroxide (152g) was dissolved in 96mL of DM water in a 3 L RBF. Methanol (48OmL) was charged at 25-300C and cooled to 0-50C. Urea (49.5g) and lOOg of Benzil was charged at 0-50C. The reaction mixture was refluxed for 60min and 144OmL of water was added to it and was cooled to 00C. 1Og of hyflo & 1Og of activated carbon was added and stirred for 30-60min at 0-5° C. The reaction mixture was filtered through hyflo bed and washed with chilled 10OmL of water and collected into a 3 L RBF. The pH was adjusted to 6.0 - 7.0 with cone, hydrochloric acid at 30-45° C. The slurry was stirred for 30min, filtered and washed with 100OmL hot water to obtain 178. Ig wet Phenytoin having moisture contents 38.7%w/w. The anhydrous weight was found to be 109.2g.Phenytoin (178g) was dissolved in 600 mL of DM water and Sodium hydroxide solution (16.7g dissolved in water 105mL) at 30-400C in a 2 L RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (2 Ig dissolved in water 32mL) was added to it. The filtrate was cooled to 5-100C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum & nitrogen atmosphere and washed with 10OmL of chilled water. The solid was dried at 50-600C under nitrogen atmosphere to obtain 102.6g of dry Phenytoin sodium. | |
In ethanol Reflux; | ||
With potassium hydroxide | ||
With sodium hydroxide In water monomer for 2h; Reflux; Large scale; | 1.1 1) Preparation of phenytoin Add 800kg of water, 200kg of diphenylethylenedione, 85kg of urea and 80kg of sodium hydroxide into a 2000L reactor, heat to reflux for 2 hours, filter after the reaction, and cool the filtrate to about 30°C and add concentrated hydrochloric acid to adjust the pH to 4 ~5, then crystallize and stir for 2 hours, shake and filter, wash the filter cake with a large amount of water, and discharge the crude phenytoin product. The resulting product is put into the beating kettle, 500kg purified water is added, and the slurry is beaten at room temperature for 2 hours, filtered and discharged Get phenytoin trendy products; | |
Stage #1: dibenzoyl; urea With potassium hydroxide In ethanol Stage #2: With sulfuric acid | ||
With potassium hydroxide In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate In water at 20℃; for 24h; | |
92% | With potassium carbonate In water for 24h; Ambient temperature; | |
With potassium carbonate In water for 24h; Ambient temperature; |
With sodium hydroxide; water In ethanol | ||
With potassium carbonate In water at 25℃; for 3h; | ||
With potassium carbonate In water at 30 - 58℃; for 1 - 2h; | 1; 8 EXAMPLE 1 PREPARATION OF 5,5-DIPHENYL-3-(TETRAHYDRO-PYRAN-2-YLOXYMETHYL)-IMIDAZOLIDINE-2,4-DIONE OF FORMULA II 390 liters of water was taken into a reactor and 0.64 kg of potassium carbonate was added. The mixture was stirred at 33° C. for 15 minutes to get a clear solution, and 14.7 kg of 40% aqueous formaldehyde was added and then stirred for 15 minutes. 13 kg of 5,5-diphenyl-2, 4-imidazolidinedione (phenytoin) was added to the solution followed by addition of 78 liters of water. The reaction mass was maintained at 30° C. for 2 hours, and reaction completion was checked using HPLC. After the reaction was completed, the reaction mass was passed through a centrifuge and the solid was washed with 52 liters of water, followed by washing with 78 liters of water in two equal lots. The wet material was dried at 57° C. for 6 hours to yield 13.5 kg of the title compound. EXAMPLE 8; PREPARATION OF 3-HYDROXYMETHYL-5,5-DIPHENYL-IMIDAZOLIDINE-2,4-DIONE (FORMULA VII); 360 ml of water was taken into a clean and dry round bottom flask containing 0.5 g of potassium carbonate. The mixture was stirred for 20 minutes. 10 g of 5,5-diphenyl-2,4-imidazolidinedione of Formula VI and 40 ml of formaldehyde were added to the above solution and the resulting mixture was heated to 57° C. The reaction mass was maintained at 57-58° C. for 1 hour, and then cooled to 30° C. The separated solid was filtered and washed with 300 ml of water followed by drying the solid obtained at 45° C. under a vacuum of 400 mm Hg for 7 hours to afford 10.1 g of the title compound. Mass (m/z)=282 a.m.u. | |
With sodium hydroxide In ethanol; water at 20℃; for 0.5h; | ||
1.35 kg | In water for 2h; Autoclave; Large scale; | 1a Preparation of 3-hydroxymethyl-5,5-diphenyl-imidazol-2,4-dione In a 50 L autoclave,Plus deionized water 39L,Potassium carbonate 64 g,Stirring,The temperature rose to 33 ° C,About 15 min,Solution clarification,Plus 40% formaldehyde solution 1. 47kg,Stir for 15 minAfter the addition of 5, 5 - diphenyl - 2, 4 - imidazole dione (phenytoin) 1.3 kg,Deionized water 7. 8 L,Stirring 2h,After completion of the reaction,The solid was washed with water (5.2 L)Vacuum 70 ° C drying 6h,To give 1.35 kg of 3-hydroxymethyl-5,5-diphenyl-imidazole-2,4-dione. |
30 kg | In ethanol at 50℃; Large scale; | 1 (Example 1)Preparation of 3-hydroxymethyl-5,5-diphenyl-2,4-imidazolidinedione 30 kg of phenytoin, 19 kg of 37% formaldehyde and 60 L of ethanol were heated to about 50 ° C. and stirred for several hours. Subsequently, the reaction product was cooled, 60 L of water was added and stirred, and the precipitated crystal was separated by filtration and washed with 60 L of ethanol. The obtained wet cake was dried under reduced pressure to obtain 3-hydroxymethyl-5,5-diphenyl-2,4-imidazolidinedione (30 kg, yield 100% by weight). |
With potassium carbonate In water at 20℃; for 24h; | 2.2.1 Synthesis of hydroxymethyl phenytoin 4 A mixture of phenytoin (1) (8.0mmol), 37% HCHO (107.0mmol) solution, and K2CO3 (0.7mmol) in H2O (72mL) was stirred at room temperature under air for 1 day. The mixture was filtered and washed with H2O to give hydroxymethyl phenytoin 4. (0020) Hydroxymethyl phenytoin 4 mp 185-187°C; IR (KBr) 3394, 3338, 1768, 1706 cm-1; 1H NMR (400MHz, CD3OD) δ 4.82 (2H, d, J=8.2Hz), 6.42 (1H, t, J=8.0Hz), 7.34-7.43 (10H, m), 9.64 (1H, s). | |
With potassium carbonate In water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 110℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With sodium hydride In dichloromethane; N,N-dimethyl-formamide at 80℃; for 7h; | |
With copper diacetate; sodium hydride 1) CH2Cl2, DMF, r.t., several hours, 2) 80 deg C, 7 h; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With hydrazine hydrate In methanol for 12h; Reflux; | |
56% | With hydrazine hydrate at 130 - 140℃; for 4h; | |
With hydrazine hydrate at 135℃; for 5h; |
With hydrazine hydrate |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With dihydrogen peroxide; sodium hydrogencarbonate at 24℃; for 0.5h; | |
99% | With tetrabromoglycoluril In ethanol at 40℃; for 0.166667h; Green chemistry; | General procedure for the oxidation of thioureas 1a - 6a to ureas 1b - 6b General procedure: Tetrabromo and tetrachloroglycoluril, 0.4 mol, was added to a solution of 1 mol of 1a - 6a in 10 mL of ethanol or methanol (Table 1). During the addition, the mixture turned light yellow. It was stirred for 10 - 25 min at 40 °C until the yellow color disappeared and filtered from the precipitate of glycoluril, the filtrate was concentrated, and the solid product was filtered off and washed with water. The products were identified by comparing their physical properties and spectral characteristics with published data. The yields of 1b - 6b are given in Table 1. 5,5-Diphenylimidazolidine-2,4-dione (1b). White solid, mp 293 - 298 °C [18, 24]. IR spectrum, ν, cm - 1: 3198 (N - H), 3070 (C - H), 1714, 1694 (C=O), 1493 (C=C) 1241 (C - N). 1H NMR spectrum, δ, ppm: 11.12 s (1H, NH), 9.33 s (1H, NH), 7.32 - 7.42 m (10H, Harom). 13C NMR spectrum, δC, ppm: 175.29, 156.46, 140.36, 128.98, 127.04, 70.67. |
92% | With dihydrogen peroxide; acetic acid In water; N,N-dimethyl-formamide at 20℃; for 24h; |
With Nitrogen dioxide for 6h; Yield given; | ||
Multi-step reaction with 2 steps 1: 75 percent / sodium ethoxide / ethanol / 4 h / 20 °C 2: 65 percent / hydrochloric acid / ethanol / 2 h / Heating | ||
Multi-step reaction with 2 steps 1: 70 percent / potassium hydroxide / ethanol / 3 h / Heating 2: 65 percent / hydrochloric acid / ethanol / 2 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: phenythoin With tetrabutylammomium bromide; sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: ethyl bromofluoroacetate In tetrahydrofuran at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | Stage #1: phenythoin With tetrabutylammomium bromide; sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: t-butyl 2-bromo-2-fluoroacetate In tetrahydrofuran at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 36h; | |
87% | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 24h; | 5,5-Diphenyl-3-(prop-2-yn-1-yl)imidazolidine-2,4-dione (3) 3-Bromoprop-1-yne (2, 1.2 mmol) was added slowly to a stirring mixture of 5,5-diphenylimidazolidine-2,4-dione (1, 1 mmol) and K2CO3(1.2 mmol) in 3 cm3 dry DMF at room temperature. Stirring was continued until the disappearance of compound 1 (monitored by TLC). The solvent was evaporated to dryness; the residue was washed with H2O and dried. White powder solid; yield 87%; m.p.: 136-138 °C (Ref.[44]: 137-138 °C). |
76% | With potassium hydroxide In ethanol for 4h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With sodium hydroxide In ethanol; water for 4h; Reflux; | 3-(2-Bromoethyl)-5,5-diphenylhydantoin (1b) To the solution of 0.8 g (20 mmol) of sodium hydroxide in 20 mL of water, 5.05 g (20 mmol) of 5,5-diphenyl hydantoin was added and heated to homogenize of the mixture, then a solution of 7.51 g (40 mmol) of 1,2-dibromoethane in 40 mL of ethanol was added and the mixture was refluxed for 4 h. After cooling, the precipitate was filtered off and dried in air. Yield 6.6 g (92%), colorless crystals, mp 150-152°C (i-PrOH) {mp 156-157°C (EtOH) [25]. IR spectrum, ν, cm-1: 3455, 3250, 3180 (N-H), 1768, 1715 (C=O), 1602, 830 (C6H5), 600 (C-Br). |
76% | With potassium hydroxide In N,N-dimethyl-formamide at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 24h; | Commercially available 5,5-diphenyl hydantoin (phenytoin, 0.50 g, 1.98 mmoles) is dissolved in dry THF (20 mL); triphenyl phosphine (0.78 g, 2.97 mmoles) and 4-hydroxy-N-benzyl piperidine (0.567 g, 2.97 mmoles) are EPO <DP n="29"/>added to the reaction mixture. The resulting solution is cooled to O0C and diethyl aza-dicarboxylate (DEAD, 0.47 mL) is added dropwise. The reaction is then stirred at room temperature for 24 hours. The solvent is evaporated under vacuum and the product is purified by chromatography on silica gel (500 g, eluent: AcOEt:hexane = 2:8 to AcOEt), to yield 0.8 g of pure product as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With sodium hydroxide; In ethanol; at 42℃; for 0.25h; | Salt formation reaction:Prepare 2.45g sodium hydroxide in ethanol solution10% sodium hydroxide ethanol solution is ready for use,Weigh 12.37g of phenytoin suspended in20mL ethanol solution,Warm to 42 C,Add NaOH ethanol solution with stirring,Stir the reaction quickly for 15 min,Add 36 mL of ice cyclohexane to room temperature.After cooling in an ice bath for 20 min, colorless needle crystals were precipitated, suction filtered, washed with a small amount of ice cyclohexane, and the cake was dried at 103 C for 1 h.Obtained a colorless needle crystal form of phenytoin 13.04g,The yield was 97.0% and the liquid phase content was 99.5%. |
~ 85 - ~ 95.3% | With sodium hydroxide; sodium chloride; In water; at 5 - 30℃; for 1.0h;Product distribution / selectivity; | Example 2; Preparation of Phenytoin Sodium in Water with Sodium chloride (20% w.r.t Phenvtoin); Phenytoin (2Og) was dissolved in 120 mL of DM water and Sodium hydroxide solution (3.56g dissolved in water 22.5mL) at 25-300C in a 250 mL four-necked RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (4g Dissolved in water 1OmL) was added to it. The reaction mass was cooled to 5-100C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum & nitrogen atmosphere and washed the product with 2OmL of chilled water. The solid was dried at 50-600C under nitrogen atmosphere to obtain 18.5g of dry Phenytoin sodium. Yield : approx. 85% w.r.t. Phenytoin; Example 3; Preparation of Phenvtoin Sodium in Water with Sodium Chloride (30% w.r.t Phenvtoin); Phenytoin (25g) was dissolved in 150 mL of DM water and Sodium hydroxide solution (4.45g dissolved in water 25mL) at 25-300C in a 250 mL four-necked RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (7.5g Dissolved in water 22mL) was added to it. The reaction mass was cooled to 5-100C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum & <n="6"/>nitrogen atmosphere and washed the product with 2OmL of chilled water. The solid was dried at 50-600C under nitrogen atmosphere to obtain 25.3g of dry Phenytoin sodium. Yield : approx. 93% w.r.t. Phenytoin; Example 4; Preparation of Phenytoin Sodium in Water with Sodium Chloride (40% w.r.t Phenvtoin); Phenytoin (25g) was dissolved in 150 mL of DM water and Sodium hydroxide solution (4.45g dissolved in water 25mL) at 25-300C in a 250 mL four-necked RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (1Og Dissolved in water 28mL) was added to it. The reaction mass was cooled to 5-100C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum & nitrogen atmosphere and washed the product with 2OmL of chilled water. The solid was dried at 50-600C under nitrogen atmosphere to obtain 25.9g of dry Phenytoin sodium. Yield: approx. 95.3% w.r.t. Phenytoin; Example 5; In-situ preparation of Phenytoin Sodium in Water with Sodium chloride (20% w.r.t phenvtoin); Potassium hydroxide (152g) was dissolved in 96mL of DM water in a 3 L RBF. Methanol (48OmL) was charged at 25-300C and cooled to 0-50C. Urea (49.5g) and lOOg of Benzil was charged at 0-50C. The reaction mixture was refluxed for 60min and 144OmL of water was added to it and was cooled to 00C. 1Og of hyflo & 1Og of activated carbon was added and stirred for 30-60min at 0-5 C. The reaction mixture was filtered through hyflo bed and washed with chilled 10OmL of water and collected into a 3 L RBF. The pH was adjusted to 6.0 - 7.0 with cone, hydrochloric acid at 30-45 C. The slurry was stirred for 30min, filtered and washed with 100OmL hot water to obtain 178. Ig wet Phenytoin having moisture contents 38.7%w/w. The anhydrous weight was found to be 109.2g.Phenytoin (178g) was dissolved in 600 mL of DM water and Sodium hydroxide solution (16.7g dissolved in water 105mL) at 30-400C in a 2 L RBF. The reaction mixture was filtered and the clear filtrate was collected and Sodium chloride solution (2 Ig dissolved in <n="7"/>water 32mL) was added to it. The filtrate was cooled to 5-100C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum & nitrogen atmosphere and washed with 10OmL of chilled water. The solid was dried at 50-600C under nitrogen atmosphere to obtain 102.6g of dry Phenytoin sodium. |
~ 66.2% | With sodium hydroxide; In water; at 5 - 30℃; for 1.0h;Product distribution / selectivity; | Example 1; Preparation of Phenytoin Sodium in Water; Phenytoin (2Og) was dissolved in 120 mL of DM water and Sodium hydroxide solution (3.56g dissolved in water 22.5mL) at 25-300C in a 250 mL four-necked RBF. The reaction mixture was filtered and the clear filtrate was collected. The reaction mass was cooled to 5-100C under nitrogen atmosphere and stirred for 60min. The solid was filtered under vacuum & nitrogen atmosphere and washed the product with 2OmL of chilled water. The solid was dried at 50-600C under nitrogen atmosphere to obtain 14.4g of dry Phenytoin sodium. Yield: approx. 66.2% w.r.t. Phenytoin |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.18 g | With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 18h; | |
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 18h; | 5.2 Commercially available 5,5-diphenyl hydantoin (phenytoin, 0.20 g, 0.793 mmoles) is dissolved in dry DMF (10 mL) and K2CO3 (0.33 g,2.38 mmoles) and tropine mesilate (prepared in the previous step), dissolved in dry DMF (3 mL) are added. The reaction is then stirred at 800C for 18 hours. The reaction mixture is diluted with water and extracted with ethyl acetate; the organic phase is washed with water, then with brine, finally dried and concentrated under vacuum to give a yellowish solid which is crystallized from ethyl ether to give the desired product as a white solid (0.18 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With formaldehyd; thionyl chloride; potassium carbonate In n-heptane; water; ethyl acetate | 1.A Step (A) Step (A) Preparation of 3-(Chloromethyl)-5,5-diphenyl-2.4-imidazolidinedione A mixture of 250 kg 5,5-diphenyl-2,4-imidazolidinedione (phenytoin), 2.6 kg of potassium carbonate, and 454 L ethyl alcohol is heated to 70° C. to 80° C. One hundred twenty-five kilograms of 37% formaldehyde solution is added, and heating is continued for at least 2 hours. The reaction mixture is cooled slowly, and 600 L of water is added during the cooling cycle. The resulting slurry is cooled to less than 25° C. The product, 3-hydroxymethyl-5,5-diphenyl-2,4-imidazolidinedione, is collected by filtration and washed with water. The wet cake is dried at 20° C. to 50° C. The dried product and 1350 kg of ethyl acetate are charged to a reactor. Five kilograms of dimethyl formamide and 135 kg of thionyl chloride are added at 25° C. to 35° C. The reaction mixture is heated to 35° C. to 60° C. for about 2 hours or until the reaction is essentially complete. The reaction mixture is cooled to 20° C. to 30° C. and combined with 2200 L of aqueous sodium bicarbonate. The organic layer is separated and concentrated by distillation. Heptane is added, and the resulting slurry is cooled. The title compoundcompound is collected by filtration and washed with heptane. The wet cake is dried at 20° C. to 50° C. under vacuum to give 3-(chloromethyl)-5,5-diphenyl-2,4-imidazolidinedione, 268 kg (90% yield); mp 161.2-161.8° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With formaldehyd In water | 5 Preparation of 5,5-Diphenyl-3-hydroxymethyl-2,4-imidazolidinedione EXAMPLE 5 Preparation of 5,5-Diphenyl-3-hydroxymethyl-2,4-imidazolidinedione Phenytoin (5 g, 0.02 mol) was suspended in 180 mL of water; 20 mL of formaldehyde (37% solution) and 0.25 g K2 CO3 were added and the mixture was stirred at 25°-30° C. for 24 hours. The white solid which formed was removed by filtration and washed repeatedly with a 3% solution of formaldehyde, then air-dried for 3 to 4 hours and over P2 O5 in a vacuum desiccator. Yield 91-93%, m.p. 185°-189° C. Anal. calc. for C16 H14 N2 O3: C, 68.07; H, 5.00; N, 9.93. Found: C, 67.97; H, 5.05., N, 9.93. The product had the formula: STR70 |
91% | With formaldehyd In water | 5 Preparation of 5,5-Diphenyl-3-hydroxymethyl-2,4-imidazolidinedione EXAMPLE 5 Preparation of 5,5-Diphenyl-3-hydroxymethyl-2,4-imidazolidinedione Phenytoin (5 g, 0.02 mol) was suspended in 180 mL of water; 20 mL of formaldehyde (37% solution) and 0.25 g K2 CO3 were added and the mixture was stirred at 25°-30° C. for 24 hours. The white solid which formed was removed by filtration and washed repeatedly with a 3% solution of formaldehyde, then air-dried for 3 to 4 hours and over P2 O5 in a vacuum dessicator. Yield 91-93%, m.p. 185°-189° C. Anal. calc. for C16 H14 N2 O3: C, 68.07; H, 5.00; N, 9.93. Found: C, 67.97; H, 5.05; N, 9.93. The product had the formula: STR69 |
91% | With formaldehyd In water | 138 Preparation of 5,5-Diphenyl-3-hydroxymethyl-2,4-imidazolidinedione EXAMPLE 138 Preparation of 5,5-Diphenyl-3-hydroxymethyl-2,4-imidazolidinedione Phenytoin (5 g, 0.02 mol) was suspended in 180 ml of water; 20 ml of formaldehyde (37% solution) and 0.25 g K2 CO3 were added and the mixture was stirred at 25°-30° C. for 24 hours. The white solid which formed was removed by filtration and washed repeatedly with a 3% solution of formaldehyde, then air dried for 3 to 4 hours and over P2 O5 in a vacuum dessicator. Yield 91-93%, m.p. 185°-189° C. Anal. calc. for C16 H14 N2 O3: C, 68.07; H, 5.00; N, 9.93. Found: C, 67.97; H, 5.05; N, 9.93. The product has the formula: STR1602 |
With formaldehyd In water | 5 Preparation of 5,5-Diphenyl-3-hydroxymethyl-2,4imidazolidinedione EXAMPLE 5 Preparation of 5,5-Diphenyl-3-hydroxymethyl-2,4imidazolidinedione Phenytoin (5 g, 0.02 mol) was suspended in 180 mL of water; 20 mL of formaldehyde (37% solution) and 0.25 g K2 CO3 were added and the mixture was stirred at 25°- 30° C. for 24 hours. The white solid which formed was removed by filtration and washed repeatedly with a 3% solution of formaldehyde, then air-dried for 3 to 4 hours and over P2 O5 in a vacuum dessicator Yield 91- 93%, m.p. 185°-189° C. Anal. calc for C16 H14 N2 O3; C, 68.07; H, 5.00; N, 9.93. Found: C, 67.97; H, 5.05; N, 9.93. The product had the formula: STR68 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | In ethanol | 2.1 (1) (1) Ethyl 3-(5,5-diphenyl-hydantoin)-acetate A solution of 12.6 g (0.05 mol) of 5,5-diphenyl-hydantoin and 6.1 ml (0.055 mol) of ethyl bromoacetate in 100 ml of absolute ethanol is heated under reflux, whilst stirring, and a solution of sodium ethylate prepared from 1.15 g (0.05 gram atom) of sodium and 100 ml of ethanol is run in dropwise over the course of 3 hours. The mixture is heated for a further hour, the sodium bromide is filtered off hot, the filtrate is cooled and the product is filtered off. 16.2 g (96% yield) of ester, melting at 184°-185° C., are obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With formaldehyd; potassium carbonate In water | 1 Example 1 Example 1 Preparation of 5,5-diphenyl-3-(hydroxymethyl) hydantoin (V) A suspension containing 10 g (39.7 mmol) of phenytoin and 0.5 g (5 mmol) of potassium carbonate in 350 ml of water and 40 ml of 35% aqueous formaldehyde was stirred at room temperature for 24 h. By filtering the reaction mixture, then washing the solid with 25 ml of water and drying it in a vacuum oven at 50 °C in the presence of phosphorus pentoxide, 10.30 g (yield 92%) of 5,5-diphenyl-3-(hydroxymethyl) hydantoin (IV) with a melting point of 289-91 °C were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: phenythoin With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 2-naphthaloyl chloride In tetrahydrofuran at 0 - 20℃; for 2.5h; | 1 Example 1; 3-(2-Naphthylcarbonyl)-5,5-diphenylimidazolidine-2,4-dione (Compound 1) Example 1 3-(2-Naphthylcarbonyl)-5,5-diphenylimidazolidine-2,4-dione (Compound 1) 0.5 g of 5,5-diphenylimidazolidine-2,4-dione was dissolved in tetrahydrofuran (5 ML), and sodium hydride (60%, in oil) (87 mg) was added at 0 °C under ice-cooling.. After stirred for 30 minutes, 2-naphthoyl chloride (415 mg) was added at 0 °C, followed by stirring at room temperature for 2.5 hours.. After water was carefully added, ethyl acetate (200 ML) was added, and the layers were separated.. The resulting organic layer was washed with a saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was distilled off.. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: phenythoin With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: naphthalene-1-carbonic acid chloride In tetrahydrofuran at 0 - 20℃; for 2.5h; | 2 Example 2; 3-Naphthylcarbonyl-5,5-diphenylimidazolidine-2,4-dione (Compound 2) Example 2 3-Naphthylcarbonyl-5,5-diphenylimidazolidine-2,4-dione (Compound 2) 0.5 g of 5,5-diphenylimidazolidine-2,4-dione was dissolved in tetrahydrofuran (5 ML), and sodium hydride (60%, in oil) (87 mg) was added at 0 °C under ice-cooling.. After stirred for 30 minutes, 1-naphthoyl chloride (396 mg) was added at 0 °C, followed by stirring at room temperature for 2.5 hours.. After water was added carefully, ethyl acetate (200 ML) was added, and the layers were separated.. The resulting organic layer was washed with a saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was distilled off.. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: phenythoin With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 2-Naphthalenesulfonyl chloride In tetrahydrofuran at 0 - 20℃; | 11 Example 11; 3-(2-Naphthylsulfonyl)-5,5-diphenylimidazolidine-2,4-dione (Compound 11) Example 11 3-(2-Naphthylsulfonyl)-5,5-diphenylimidazolidine-2,4-dione (Compound 11) 5,5-Diphenylimidazolidine-2,4-dione (0.5 g) was dissolved in tetrahydrofuran (5 ML), and sodium hydride (60%, in oil) (87 mg) was added at 0 °C under ice-cooling.. After stirred for 30 minutes, 2-naphthalenesulfonyl chloride (471 mg) was added at 0 °C, and the mixture was stirred at room temperature overnight.. After water was added carefully, ethyl acetate (100 ML) was added, and the layers were separated.. The resulting organic layer was washed with a saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was distilled off.. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: phenythoin With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 2-furancarbonyl chloride In tetrahydrofuran at 0 - 20℃; for 2.5h; | 10 Example 10; 3-(2-Furylcarbonyl)-5,5-diphenylimidazolidine-2,4-dione (Compound 10) Example 10 3-(2-Furylcarbonyl)-5,5-diphenylimidazolidine-2,4-dione (Compound 10) 5,5-Diphenylimidazolidine-2,4-dione (0.5 g) was dissolved in tetrahydrofuran (5 ML), and sodium hydride (60%, in oil) (87 mg) was added at 0 °C under ice-cooling.. After stirred for 30 minutes, 2-furoyl chloride (235 mg) was added 0 °C, and the mixture was stirred at room temperature for 2.5 hours.. After water was added carefully, ethyl acetate (200 ML) was added, and the layers were separated.. The resulting organic layer was washed with a saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was distilled off.. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: phenythoin With sodium hydride In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 1-Naphthalenesulfonyl chloride In tetrahydrofuran at 0 - 20℃; | 12 Example 12; 3-Naphthylsulfonyl-5,5-diphenylimidazolidine-2,4-dione (Compound 12) Example 12 3-Naphthylsulfonyl-5,5-diphenylimidazolidine-2,4-dione (Compound 12) 5,5-Diphenylimidazolidine-2,4-dione (0.5 g) was dissolved in tetrahydrofuran (5 ML), and sodium hydride (60%, in oil) (87 mg) was added at 0 °C under ice-cooling.. After stirred for 30 minutes, 1-naphthalenesulfonyl chloride (471 mg) was added at 0 °C, and the mixture was stirred at room temperature overnight.. After water was added carefully, ethyl acetate (100 ML) was added, and the layers were separated.. The resulting organic layer was washed with a saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was distilled off.. The material was dissolved in ethyl acetate, and purified by silica gel chromatography (hexane:ethyl acetate=3:1 to 2:1) to obtain 100 mg of white powder.1H-NMR (CDCl3+CD3OD) δ7.13-7.37 (9H, m), 7.49-7.64 (4H, m), 7.95 (1H, m), 8.17 (1H, m), 8.53 (1H, m), 8.64 (1H, m).13C-NMR (CDCl3+CD3OD) δ70.2, 123.3, 124.2, 127.0, 127.3, 128.5, 128.8, 129.4, 129.7, 132.2, 133.1, 134.0, 136.6, 138.2, 151.1, 169.8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 98% 2: 1.6% | With sodium hydroxide for 0.0333333h; Microwave irradiation; neat (no solvent); | |
1: 75% 2: 14% | With potassium hydroxide In ethanol at 40℃; for 2h; Ultrasound irradiation; | |
61% | With potassium hydroxide In methanol at 64.84℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide In ethanol | ||
With potassium carbonate In acetonitrile for 4h; Reflux; | 5 ,5-Diphenylhydantoin (0.500 g, 1.982 mmol) was dissolved in acetonitrile and benzyl bromide (0.236 ml, 1.982 mmol) was added to the flask. Potassium carbonate (0.274 g, 1.982 mmol) was added and reaction allowed to stir at reflux for four hours. The reaction was monitored using HPLC at which point an additional 150 mL DCM was added. The organic layer was washed with water and dried over Na2SO4. The solvent was removed under reduced pressure. The product was purified by Biotage and characterized by LC/MS and NMR |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With tungsten hexacarbonyl; iodine; 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 35℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: phenythoin With triethylamine In dichloromethane at 20℃; for 0.25h; Stage #2: trityl chloride In dichloromethane | 1 General Procedure for the Synthesis of 5,5-diphenyl-3-tritylimidazolidine-2,4-dione (Compound 2) General procedure: General Procedure for the Synthesis of 5,5-diphenyl-3-tritylimidazolidine-2,4-dione (Compound 2) A mixture of 5,5-diphenylhydantoin (Compound 1) (2.522 g, 10 mmol) was dissolved in 30 mL dichloromethylene ("DCM"). Triethylamine (2.79 mls, 20 mmol) was added and the solution stirred at room temperature for 15 minutes. Trityl chloride (4.18 g, 15 mmol) was dissolved in 30 mL DCM and slowly added to the reaction mixture. The solution was allowed to stir overnight and HPLC was used to monitor the reaction. The resulting solution was washed with 250 mL water and 250 mL diluted 1% NaOH solution. The organic phase was collected and dried over sodium sulfate. The solvent was removed under reduced pressure. The desired product (Compound 2) was obtained as a white solid by crystallization from 1-butanol. (Yield ˜93%) |
58% | With triethylamine In dichloromethane at 20℃; for 30h; | 4.1.1. Preparation of 5,5-diphenyl-3-tritylimidazolidine-2,4-dione (24) A mixture of 23 (50 mmol, 12.6 g) in CH2Cl2 (80 mL) and TEA (100 mmol, 10 g) in CH2Cl2 (40 mL) was stirred in room temperature for 15 min. Trityl chloride (50 mmol, 13.9 g) in CH2Cl2 (300 mL) was slowly added (10 min). The reactants were mixed in room temperature for 30 h. The solution was washed with water (250 mL) and twice with diluted NaOH solution (1%, 250 mL). The organic phase was dried with anhydrous Na2SO4. After evaporation of the solvent, the residue was crystallized from 1-butanol giving pure white crystals of 24 (14.6 g, 29 mmol, 58%) mp 252-253 °C, Rf (I): 0.49. 1H NMR for 24 (DMSO-d6) δ (ppm): 7.03-7.08 (m, 4H, 2 × 5-Ph-3,5-H), 7.15-7.38 (m, 21H, 2 × 5-Ph-2,4,6-H, 3 × Phtrityl), 9.47 (s, 1H, NH). Anal. Calcd for C34H26N2O2: C, 82.57; H, 5.30; N, 5.67. Found: C, 82.78; H, 5.31; N, 5.40. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: < 20 %Chromat. 2: 68% | Stage #1: phenythoin With sodium bis(2-methoxyethoxy)aluminium dihydride In toluene for 24h; Reflux; Stage #2: With water; sodium hydroxide In toluene at 0℃; | General procedure: A representative experiment: 2,2-diphenylaziridine (3; R1 = Ph, R2 = Ph, R3 = H): To a stirred slurry of 5,5-diphenylhydantoin (1 mmol, 254 mg) in dry toluene (1 mL) under argon at rt was added Red-Al in toluene (3.5 M, 5 mmol, 1.43 mL) over 20 min. CAUTION: excessive foaming, gas and heat evolution. When the initial reaction had subsided, the temperature was slowly increased to reflux (oil bath at 120 °C) and the mixture maintained at this temperature for 24 h. The mixture was cooled to 0 °C and the reaction quenched by careful addition of aqueous NaOH (2 M, 5 mL), followed by CH2Cl2 (5 mL). The resulting biphasic mixture was stirred at rt for 1 h before the organic phase was separated (Sorbent Phase Separator) and evaporated. The residue was slurried in MeOH (5 mL) and added to a 6 cc PoraPak Rxn CX Retained Base column. The column was flushed with methanol (10 mL), after which the product was eluted with methanolic NH3 (7 M, 10 mL). The collected fraction was evaporated to give oil, which under high vacuum gave a white solid. Yield: 132 mg (68%).1H NMR (500 MHz, DMSO-d6) δ 1.96 (s, 2H), 3.26 (s, 1H), 7.10-7.41 (m, 10H)13C NMR (125 MHz, CDCl3) δ 29.1, 46.5, 126.4, 127.6, 128.0, 145.3MS (ES): m/z [M+H]+ 196.1 (100) HRMS: m/z calcd for C14H14N [M+H]+: 196.1126; found: 196.1129. refText |
1: 70 %Chromat. 2: 30 %Chromat. | Stage #1: phenythoin With sodium bis(2-methoxyethoxy)aluminium dihydride In toluene at 100℃; for 1h; Stage #2: With water; sodium hydroxide In toluene at 0℃; | General procedure: A representative experiment: 2,2-diphenylaziridine (3; R1 = Ph, R2 = Ph, R3 = H): To a stirred slurry of 5,5-diphenylhydantoin (1 mmol, 254 mg) in dry toluene (1 mL) under argon at rt was added Red-Al in toluene (3.5 M, 5 mmol, 1.43 mL) over 20 min. CAUTION: excessive foaming, gas and heat evolution. When the initial reaction had subsided, the temperature was slowly increased to reflux (oil bath at 120 °C) and the mixture maintained at this temperature for 24 h. The mixture was cooled to 0 °C and the reaction quenched by careful addition of aqueous NaOH (2 M, 5 mL), followed by CH2Cl2 (5 mL). The resulting biphasic mixture was stirred at rt for 1 h before the organic phase was separated (Sorbent Phase Separator) and evaporated. The residue was slurried in MeOH (5 mL) and added to a 6 cc PoraPak Rxn CX Retained Base column. The column was flushed with methanol (10 mL), after which the product was eluted with methanolic NH3 (7 M, 10 mL). The collected fraction was evaporated to give oil, which under high vacuum gave a white solid. Yield: 132 mg (68%).1H NMR (500 MHz, DMSO-d6) δ 1.96 (s, 2H), 3.26 (s, 1H), 7.10-7.41 (m, 10H)13C NMR (125 MHz, CDCl3) δ 29.1, 46.5, 126.4, 127.6, 128.0, 145.3MS (ES): m/z [M+H]+ 196.1 (100) HRMS: m/z calcd for C14H14N [M+H]+: 196.1126; found: 196.1129. refText |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In ethanol; water Heating; | |
85% | With iron(III) oxide In neat (no solvent) at 70℃; for 0.9h; | 4.1 General procedure for the synthesis of 5,5-disubstituted hydantoins (4a-m) by Fe3O4 nanoparticles General procedure: In a 50-mL round-bottomed flask were poured aldehyde or ketone (1 mmol), potassium cyanide (1.3 mmol),ammonium carbonate (6 mmol), and magnetic Fe3O4nanoparticles (1 mol%) sequentially. The suspension was stirred at 70 8C in solvent-free conditions. The progress ofthe reaction was monitored by TLC (petroleum ether:ethylacetate, 1:1.2 v/v). Upon completion, the mixture was cooled to room temperature and neutralized with diluted hydrochloric acid. Then, the magnetic catalyst was removed by an external magnet and reused. The obtained product was purified by crystallization from water-ethanol. The structure of the products was characterized by comparison of their physical and spectra data with those previously reported. |
84% | In ethanol; water for 0.166667h; Microwave irradiation; | General Procedure for Synthesis of 5,5-Disubstituted HydantoinsUnder Conventional Heating Conditions General procedure: All of 5,5-disubstituted hydantions were synthesized by the method of Bucherer-Bergs shown in Scheme 1. Following this procedure, 5 mmol of aldehyde or ketone was dissolved in 7mL of 50% ethanol. The freshly powdered ammoniumcarbonate (2.40 g) and 0.42 g of potassium cyanide (6.5 mmol) were dissolved in 7mL H2O. The mixture was placed in a round-bottomed flask. The reactants were mixed and irradiated at microwave oven for the period as indicated in Table 1. The progress of the reaction was monitored by thin-layer chromatography (TLC, ethyl acetate=petroleum ether1:1.3 v=v). After the completion, the reaction mixture was chilled in an ice bath. The solution was neutralized with diluted hydrochloric acid. The solvent was removed under reduced pressure. The product was collected by filtrationand washed with EtOH=H2O (1:1). The product was dried and recrystallized from 95% ethanol. The products were identified by comparing their physical andspectral data with those of authentic samples. |
In ethanol at 60℃; for 15h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In N,N-dimethyl-formamide Microwave irradiation; | |
87% | In ethanol Reflux; | General procedure for the preparation of final compounds3-18 General procedure: A total of 0,005molof5,5-di(propan-2-yl)imidazolidine-2,4-dioneor5,5-diphenylimidazolidine-2,4-dionewere dissolved in 96% ethanol, 0,005molof formaldehyde and corresponding solution of 0.005mol4-substitutedpiperazinesin 96%ethanol, were added. The reaction was refluxed for 6-12 h. Thereafter, precipitated crude products were washed with cool ethanol and separated by filtration. The final compounds were purified by recrystallization from 96% ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium carbonate In acetone at 20℃; for 24h; | |
With potassium carbonate In acetonitrile Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | Stage #1: phenythoin With potassium carbonate In acetone at 20℃; for 0.333333h; Stage #2: p-chlorophenacyl chloride In acetone at 20℃; for 24.33h; | |
43% | Stage #1: phenythoin With potassium carbonate In acetone at 20℃; for 0.5h; Stage #2: p-chlorophenacyl chloride In acetone at 20℃; for 24h; | 8 2.1.2. General procedure for the preparation of 1h, 1i, 2h, 2i, 3h, 3i General procedure: The compounds 1h, 1i, 2h, 2i, 3h and 3i were prepared according to the procedure given in Ref. [21] (Scheme 2). A mixtureof the appropriate hydantoin (cycloalkanespiro-5-hydantoin or 5,5-diphenylhydantoin) (0.01 mol) and potassium carbonate (0.01 mol)was stirred in acetone (60 cm3) at room temperature for half anhour. A solution of 1-(4-substituted phenyl)-2-chloroethanone(0.011 mol) in acetone was added and the reaction mixture wasstirred for 24 h at room temperature. The obtained solid wasfiltered and recrystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: phenythoin With potassium carbonate In acetone at 20℃; for 0.333333h; Stage #2: 2-Chloro-4'-fluoroacetophenone In acetone at 20℃; for 24.33h; | |
45% | Stage #1: phenythoin With potassium carbonate In acetone at 20℃; for 0.5h; Stage #2: 2-Chloro-4'-fluoroacetophenone In acetone at 20℃; for 24h; | 8 2.1.2. General procedure for the preparation of 1h, 1i, 2h, 2i, 3h, 3i General procedure: The compounds 1h, 1i, 2h, 2i, 3h and 3i were prepared according to the procedure given in Ref. [21] (Scheme 2). A mixtureof the appropriate hydantoin (cycloalkanespiro-5-hydantoin or 5,5-diphenylhydantoin) (0.01 mol) and potassium carbonate (0.01 mol)was stirred in acetone (60 cm3) at room temperature for half anhour. A solution of 1-(4-substituted phenyl)-2-chloroethanone(0.011 mol) in acetone was added and the reaction mixture wasstirred for 24 h at room temperature. The obtained solid wasfiltered and recrystallized from ethanol. |
With potassium carbonate In acetone at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With methanesulfonic acid In dichloromethane at 60℃; for 24h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium carbonate In acetone at 20℃; for 24h; | 1 General procedure for the synthesis of compounds 2-10 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-2-chloroacetamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry acetone (10mL) was stirred at room temperature for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the solid obtained was washed with water, dried and re-crystallized from an appropriate solvent. 4.1.1.1 2-(2,5-Dioxo-4,4-diphenylimidazolidin-1-yl)-N-phenylacetamide (2) [44]. (0021) White powder, Mp 245-247οC (Lit. 246-247οC) [44], 88% yield (CH3H2OH/CH2Cl2); IR (KBr, cm-1) ν: 3198 (NH), 1772, 1717 (C=O); 1H NMR (500MHz, DMSO-d6): δ 4.33 (s, 2H), 7.06-7.09 (t, 1H, J=7.0Hz), 7.31-7.45 (m, 12H), 7.59-7.60 (d, 2H, J=8.0Hz), 9.71 (s, 1H), 10.43 (s, 1H); 13C NMR (125MHz, DMSO-d6): δ 41.02, 69.50, 119.09, 123.50, 126.56, 126.95, 128.16, 128.45, 128.81, 138.55, 139.61, 154.96, 164.54, 173.40; C23H19N3O3: m/z (385.4). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium carbonate; In acetone; at 20℃; for 24h; | General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-2-chloroacetamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry acetone (10mL) was stirred at room temperature for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the solid obtained was washed with water, dried and re-crystallized from an appropriate solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With potassium carbonate In acetone at 20℃; for 24h; | 3 General procedure for the synthesis of compounds 2-10 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-2-chloroacetamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry acetone (10mL) was stirred at room temperature for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the solid obtained was washed with water, dried and re-crystallized from an appropriate solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate In acetone at 20℃; for 24h; | 4 General procedure for the synthesis of compounds 2-10 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-2-chloroacetamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry acetone (10mL) was stirred at room temperature for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the solid obtained was washed with water, dried and re-crystallized from an appropriate solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium carbonate In acetone at 20℃; for 24h; | 5 General procedure for the synthesis of compounds 2-10 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-2-chloroacetamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry acetone (10mL) was stirred at room temperature for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the solid obtained was washed with water, dried and re-crystallized from an appropriate solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate In acetone at 20℃; for 24h; | 2 General procedure for the synthesis of compounds 2-10 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-2-chloroacetamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry acetone (10mL) was stirred at room temperature for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the solid obtained was washed with water, dried and re-crystallized from an appropriate solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With potassium carbonate In acetone at 20℃; for 24h; | 7 General procedure for the synthesis of compounds 2-10 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-2-chloroacetamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry acetone (10mL) was stirred at room temperature for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the solid obtained was washed with water, dried and re-crystallized from an appropriate solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate In acetone at 20℃; for 24h; | 8 General procedure for the synthesis of compounds 2-10 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-2-chloroacetamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry acetone (10mL) was stirred at room temperature for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the solid obtained was washed with water, dried and re-crystallized from an appropriate solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate In acetone at 20℃; for 24h; | 9 General procedure for the synthesis of compounds 2-10 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-2-chloroacetamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry acetone (10mL) was stirred at room temperature for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the solid obtained was washed with water, dried and re-crystallized from an appropriate solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium carbonate; In N,N-dimethyl-formamide; at 50℃; for 24h; | General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-3-chloropropanamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry DMF (10mL) was stirred at 50οC for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the precipitate obtained was washed with water, dried and re-crystallized from an appropriate solvent. 4.1.2.1 3-(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)-N-phenylpropanamide (11) (0031) White powder, M.p 297-299οC, 89% yield (CH3OH/CH2Cl2); IR (KBr, cm-1) ν: 3190 (NH), 1769, 1721 (C=O); 1H NMR (500MHz, DMSO-d6): δ 1.68-1.70 (d, 3H, J=7.0Hz), 4.77-4.79 (d, 1H, J=7.5Hz), 7.07 (s, 1H), 7.32-7.42 (m, 12H), 7.57-7.59 (d, 2H, J=8.0Hz), 9.68 (s, 1H), 10.02 (s, 1H); 13C NMR (125MHz, DMSO-d6): δ 15.42, 50.73, 69.24, 120.16, 124.04, 127.29, 127.55, 128.57, 128.60, 128.92, 128.94, 129.16, 139.15, 140.17, 140.39, 155.54, 168.03, 173.81; C24H21N3O3: m/z (399.3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 24h; | 2 General procedure for the synthesis of compounds 11-17 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-3-chloropropanamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry DMF (10mL) was stirred at 50οC for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the precipitate obtained was washed with water, dried and re-crystallized from an appropriate solvent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 24h; | 3 General procedure for the synthesis of compounds 11-17 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-3-chloropropanamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry DMF (10mL) was stirred at 50οC for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the precipitate obtained was washed with water, dried and re-crystallized from an appropriate solvent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 24h; | 4 General procedure for the synthesis of compounds 11-17 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-3-chloropropanamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry DMF (10mL) was stirred at 50οC for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the precipitate obtained was washed with water, dried and re-crystallized from an appropriate solvent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 24h; | 5 General procedure for the synthesis of compounds 11-17 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-3-chloropropanamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry DMF (10mL) was stirred at 50οC for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the precipitate obtained was washed with water, dried and re-crystallized from an appropriate solvent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 24h; | 6 General procedure for the synthesis of compounds 11-17 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-3-chloropropanamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry DMF (10mL) was stirred at 50οC for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the precipitate obtained was washed with water, dried and re-crystallized from an appropriate solvent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With potassium carbonate In N,N-dimethyl-formamide at 50℃; for 24h; | 7 General procedure for the synthesis of compounds 11-17 General procedure: A mixture of 5,5-diphenylimidazolidine-2,4-dione (1) (1.0mmol, 0.252gm), N-aryl-3-chloropropanamide (1.2mmol) and anhydrous potassium carbonate (2.0mmol, 0.276gm) in dry DMF (10mL) was stirred at 50οC for 24h. The reaction mixture was filtered off, the solvent was removed under reduced pressure and the precipitate obtained was washed with water, dried and re-crystallized from an appropriate solvent |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | Stage #1: phenythoin With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 0.5h; Stage #2: 1,3-dibromo-propane In dichloromethane for 3h; Reflux; | 3-(3-Bromopropyl)-5,5-diphenylimidazolidine-2,4-dione (5) DBU (1,8-diazabicycloundec-7-ene, 3.80 mL;25.0 mmol) was added dropwise to a solution of5,5-diphenylimidazolidine-2,4-dione 1 (6.30 g; 25.0 mmol)in CH2Cl2 (30 mL). After stirring for 30 minutes at roomtemperature, 1,3-dibromopropane (5.1 mL; 50.0 mmol)was added and the reaction mixture refluxed for 3 h. ThenCH2Cl2 (50 mL) was added to the reaction mixture and theorganic phase was washed with distilled water (20 mL), brine (20 mL), dried over Na2SO4 and concentrated undervacuum. The crude residue was purified by recrystallization(EtOH) yielding a white solid (6.50 g; 17.4 mmol; 69%);mp 140-144 °C; IR (KBr) ν / cm-1 3454, 3406, 3220,3099, 1772, 1706, 1494, 1417, 1255, 789, 700, 693, 518;1H NMR (300 MHz, CDCl3) d 7.36 (s, 10H), 7.14 (s, 1H),3.72 (t, 2H, J 6.9), 3.34 (t, 2H, J 6.7), 2.16-2.25 (m, 2H);13C NMR (75.46 MHz, CDCl3) d 173.2, 156.7, 138.9, 128.7,128.5, 126.6, 70.0, 37.6, 31.0, 29.5; HRMS m/z, calc. forC18H18BrN2O2 [M + H]+: 373.0552; found: 373.0549. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; | Generalprocedure for the synthesis of 10 and 11a-e General procedure: To a solution of Boc-proctected amino acid (2 mmol) and drug with an amino/hydroxy group (1mmol) in dimethylformamide (DMF, 10 mL), EDC (2.4 mmol) was added and stirredat room temperature. DMAP (0.15 mmol) was added to the solution quarter an hour later and stirred for 12-24 h at room temperature. The reaction solution was concentrated at reduced pressure using a rotary evaporator, and then diluted with EtOAc. The EtOAc solution was washed with 2% HCl aq., saturated NaHCO3 aq., and dried over anhydrous magnesium sulfate. After the concentration by rotary evaporator, the crude material was purified by silica gel chromatography (hexane-EtOAc) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; | Generalprocedure for the synthesis of 10 and 11a-e General procedure: To a solution of Boc-proctected amino acid (2 mmol) and drug with an amino/hydroxy group (1mmol) in dimethylformamide (DMF, 10 mL), EDC (2.4 mmol) was added and stirredat room temperature. DMAP (0.15 mmol) was added to the solution quarter an hour later and stirred for 12-24 h at room temperature. The reaction solution was concentrated at reduced pressure using a rotary evaporator, and then diluted with EtOAc. The EtOAc solution was washed with 2% HCl aq., saturated NaHCO3 aq., and dried over anhydrous magnesium sulfate. After the concentration by rotary evaporator, the crude material was purified by silica gel chromatography (hexane-EtOAc) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; | Generalprocedure for the synthesis of 10 and 11a-e General procedure: To a solution of Boc-proctected amino acid (2 mmol) and drug with an amino/hydroxy group (1mmol) in dimethylformamide (DMF, 10 mL), EDC (2.4 mmol) was added and stirredat room temperature. DMAP (0.15 mmol) was added to the solution quarter an hour later and stirred for 12-24 h at room temperature. The reaction solution was concentrated at reduced pressure using a rotary evaporator, and then diluted with EtOAc. The EtOAc solution was washed with 2% HCl aq., saturated NaHCO3 aq., and dried over anhydrous magnesium sulfate. After the concentration by rotary evaporator, the crude material was purified by silica gel chromatography (hexane-EtOAc) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; aq. phosphate buffer; acetonitrile; at 37℃; for 1h;pH 7.4; | General procedure: Generalprocedure: Methanol-CH3CN (1:1) solutions of prodrugs 2-5 and 7-9 (50muL) were mixed with 450 muL of phosphate-buffered saline (PBS, pH 7.4) and incubated at 37 C for 1 h, respectively. The solutions were concentrated using a rotary evaporator, and the residues were suspended in methanol. After membrane filtration (pore size 0.45 mum), the respective products released from the prodrugs wereidentified using ESI-mass spectrometry. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: bis(trichloromethyl) carbonate; phenythoin With dmap In tetrahydrofuran at 0℃; for 0.5h; Stage #2: triethylene glucol monomethyl ether In tetrahydrofuran at 20 - 60℃; | 2 Synthesis of mPEGn-Carbamate-Phenyloin Compounds General procedure: (0192) Briefly, in a 250 mL round bottom flask 5,5-diphenylhydantoin (0.252 g, 0.999 mmol) was dissolved in anhydrous THF (tetrahydrofuran). DMAP (4-dimethylaminopyridine, 0.122 g, 0.999 mmol) was added and the reaction mixture cooled to 0° C. After cooling, triphosgene (0.296 g, 0.999 mmol) was added and the reaction stirred for 30 minutes. The flask was then warmed to room temperature and charged with mPEG3-OH (246 mg, 1.498 mmol). The reaction was allowed to stir overnight at 60° C. HPLC was used to monitor the reaction mixture. Upon reaction completion an additional 150 mL DCM was added. The organic layer was washed with water (100 mL) and dried over Na2SO4. The solvent was removed under reduced pressure. Both LC/MS and NMR confirmed the presence Compound 2a (which was relatively unstable and did decompose upon purification). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium <i>tert</i>-butylate In tetrahydrofuran at 60℃; | 4 Briefly, in a 250 mL round bottom flask 5,5-diphenylhydantoin (0.252 g, 0.999 mmol) was dissolved in anhydrous THF and the reaction heated to 60° C. Then, potassium t-butoxide in THF (0.137 ml) was charged to the flask and mPEG3-Br (0.227 g, 0.999 mmol) was added. The reaction was allowed to stir overnight at 60° C. HPLC was used to monitor the reaction and upon reaction completion an additional 150 mL DCM was added. The organic layer was washed with water and dried over Na2SO4. The solvent was removed under reduced pressure. Both LC/MS and NMR confirmed the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: phenythoin With sodium hydroxide In water at 20℃; Stage #2: epichlorohydrin In water at 20℃; for 24h; | 4.1.1 General procedure for synthesis of (oxiran-2-ylmethyl)imidazolidine-2,4-diones (27-34) General procedure: An appropriated hydantoin (5.0mmol) was suspended in water (∼10mL) followed by addition of sodium hydroxide (5.0mmol) in one portion. The solution was stirred at room temperature until dissolution of the reagents. Then, 2-(chloromethyl)oxirane (5.0mmol) was added and the reaction mixture was stirred for 24h at room temperature. Progress of the reaction was monitored by thin layer chromatography (TLC) in methylene chloride/methanol 9:1. If precipitate occurred, the reaction mixture was filtered giving the desired product (Method A). Otherwise, the product was extracted from water phase with DCM. The resulting organic phase was washed with brine, filtered, dried over Na2SO4 and concentrated under a vacuum to provide a crude product. The desired product was purified with column chromatography using DCM/MeOH (98:2→95:5) as the eluent (Method B). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With triethylamine In dimethyl sulfoxide at 80℃; | 2.2. Synthesis. General procedure: Fluoroquinolone-boron complex 2 was synthesized according to Leyva et al. method [24].332.85 μmol of the fluoroquinolone 2 and 0.5 mmol ofthe heterocycle (3,5-diethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine, uracil, 5,5-diphenylhydantoine, benzimidazole or1,2,3,4-tetrahydrocarbazole) were added in 1.5mLof DMSO (for 3a-d, f ) or CH3CN (for 3e) and 69.4 μL ofTEA solution. .eir action mixture was stirred and heated at 80°C and monitored with thin layer chromatography untilreaction was completed. .en, 1mL of ethanol was added toobtain a solid, which was filtered, washed with cold ethanol,and recrystallized with CH3CN. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | In ethanol Reflux; | General procedure for the preparation of final compounds3-18 General procedure: A total of 0,005molof5,5-di(propan-2-yl)imidazolidine-2,4-dioneor5,5-diphenylimidazolidine-2,4-dionewere dissolved in 96% ethanol, 0,005molof formaldehyde and corresponding solution of 0.005mol4-substitutedpiperazinesin 96%ethanol, were added. The reaction was refluxed for 6-12 h. Thereafter, precipitated crude products were washed with cool ethanol and separated by filtration. The final compounds were purified by recrystallization from 96% ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In ethanol Reflux; | General procedure for the preparation of final compounds3-18 General procedure: A total of 0,005molof5,5-di(propan-2-yl)imidazolidine-2,4-dioneor5,5-diphenylimidazolidine-2,4-dionewere dissolved in 96% ethanol, 0,005molof formaldehyde and corresponding solution of 0.005mol4-substitutedpiperazinesin 96%ethanol, were added. The reaction was refluxed for 6-12 h. Thereafter, precipitated crude products were washed with cool ethanol and separated by filtration. The final compounds were purified by recrystallization from 96% ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | In ethanol Reflux; | General procedure for the preparation of final compounds3-18 General procedure: A total of 0,005molof5,5-di(propan-2-yl)imidazolidine-2,4-dioneor5,5-diphenylimidazolidine-2,4-dionewere dissolved in 96% ethanol, 0,005molof formaldehyde and corresponding solution of 0.005mol4-substitutedpiperazinesin 96%ethanol, were added. The reaction was refluxed for 6-12 h. Thereafter, precipitated crude products were washed with cool ethanol and separated by filtration. The final compounds were purified by recrystallization from 96% ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | In ethanol Reflux; | General procedure for the preparation of final compounds3-18 General procedure: A total of 0,005molof5,5-di(propan-2-yl)imidazolidine-2,4-dioneor5,5-diphenylimidazolidine-2,4-dionewere dissolved in 96% ethanol, 0,005molof formaldehyde and corresponding solution of 0.005mol4-substitutedpiperazinesin 96%ethanol, were added. The reaction was refluxed for 6-12 h. Thereafter, precipitated crude products were washed with cool ethanol and separated by filtration. The final compounds were purified by recrystallization from 96% ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In ethanol Reflux; | General procedure for the preparation of final compounds3-18 General procedure: A total of 0,005molof5,5-di(propan-2-yl)imidazolidine-2,4-dioneor5,5-diphenylimidazolidine-2,4-dionewere dissolved in 96% ethanol, 0,005molof formaldehyde and corresponding solution of 0.005mol4-substitutedpiperazinesin 96%ethanol, were added. The reaction was refluxed for 6-12 h. Thereafter, precipitated crude products were washed with cool ethanol and separated by filtration. The final compounds were purified by recrystallization from 96% ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With caesium carbonate In acetonitrile at 20℃; for 6h; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With caesium carbonate In acetonitrile at 20℃; for 6h; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate In dimethyl sulfoxide at 80℃; for 19h; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.4% | With urea; sodium hydroxide In ethanol; water at 80℃; for 3h; Large scale; | 1.2; 1.2; 2.2; 2; 3.2; 3; 4.2; 5; 6 (2) Rearrangement reaction Add 360 kg of reverse osmosis water and 63 kg of sodium hydroxide to the reaction tank, and after mixing, add 240 kg of absolute ethanol, 60 kg of urea, and 130 kg of benzophenone. After raising the temperature to reflux 80°C, reflux for 3 hours. Add 6kg of medicinal charcoal when the temperature is lowered to 50°C, and then decolorize when the temperature is increased to 70°C for 1 hour. After removing charcoal, the temperature was lowered to 20°C for 1.5 hours, and diluted hydrochloric acid was added dropwise to adjust the pH to 4.8, cultivate the crystals for 2 hours, centrifuge the material (800rpm, 60min) to obtain phenytoin, and dry at 85°C to obtain 143kg of phenytoin, detected by HPLC: tR=3.99min, and the purity was 99.5% by weight. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: phenythoin With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 0.05h; Stage #2: methyl iodide In tetrahydrofuran at 20℃; for 0.0833333h; | General Procedure: Methylation of Phenytoin (1a) Using tBuOK (Table 1, run 8) To a solution of phenytoin (1a, 100 mg, 0.40 mmol) in THF (2.0 mL), tBuOK (Aldrich, 1 M solution in THF, 0.80 mL, 0.80 mmol) was added at r.t. After 3 min, CH3I (30 µL, 0.48 mmol) in THF (0.1 mL) was added at r.t. and the mixture was stirred at r.t. for 5 min. One molar HCl (2 mL) was added and the whole was extracted with AcOEt (2×10, 1×5 mL). The combined organic layer was washed with brine (1×5 mL) and dried over Na2SO4. The solvent was evaporated in vacuo, and the crude product was purified by column chromatography (n-hexane-AcOEt 2 : 1) to give 4a as colorless solids (83 mg, 79%). 1-Methyl-5,5-diphenylimidazolidine-2,4-dione (4a) Colorless solids. mp 216.5-218.0 °C (lit13) 223-224 °C). IR (KBr) ν (cm-1) 3024, 1768, 1703. 1H-NMR (500 MHz, CDCl3) δ (ppm) 2.77 (3H, s, CH3), 7.26-7.31 (4H, m, Ar-H), 7.38-7.42 (6H, m, Ar-H), 9.31 (1H, s, NH). 13C-NMR (125 MHz, CDCl3) δ (ppm) 26.4, 75.8, 128.2, 128.8, 128.9, 136.1, 155.9, 174.1. High resolution electrospray ionization (HRESI) MS m/z 267.1130 (Calcd for C16H14N2O2: 267.1134). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 44% 2: 28% | Stage #1: phenythoin With 18-crown-6 ether; potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 0.05h; Stage #2: methyl iodide In tetrahydrofuran at 20℃; for 0.0833333h; | General Procedure: Methylation of Phenytoin (1a) Using tBuOK (Table 1, run 8) General procedure: To a solution of phenytoin (1a, 100 mg, 0.40 mmol) in THF (2.0 mL), tBuOK (Aldrich, 1 M solution in THF, 0.80 mL, 0.80 mmol) was added at r.t. After 3 min, CH3I (30 µL, 0.48 mmol) in THF (0.1 mL) was added at r.t. and the mixture was stirred at r.t. for 5 min. One molar HCl (2 mL) was added and the whole was extracted with AcOEt (2×10, 1×5 mL). The combined organic layer was washed with brine (1×5 mL) and dried over Na2SO4. The solvent was evaporated in vacuo, and the crude product was purified by column chromatography (n-hexane-AcOEt 2 : 1) to give 4a as colorless solids (83 mg, 79%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 53% 2: 4% | Stage #1: phenythoin With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 0.05h; Stage #2: benzyl bromide In tetrahydrofuran at 20℃; for 6h; | General Procedure: Methylation of Phenytoin (1a) Using tBuOK (Table 1, run 8) General procedure: To a solution of phenytoin (1a, 100 mg, 0.40 mmol) in THF (2.0 mL), tBuOK (Aldrich, 1 M solution in THF, 0.80 mL, 0.80 mmol) was added at r.t. After 3 min, CH3I (30 µL, 0.48 mmol) in THF (0.1 mL) was added at r.t. and the mixture was stirred at r.t. for 5 min. One molar HCl (2 mL) was added and the whole was extracted with AcOEt (2×10, 1×5 mL). The combined organic layer was washed with brine (1×5 mL) and dried over Na2SO4. The solvent was evaporated in vacuo, and the crude product was purified by column chromatography (n-hexane-AcOEt 2 : 1) to give 4a as colorless solids (83 mg, 79%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | Stage #1: phenythoin With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 0.05h; Stage #2: allyl bromide In tetrahydrofuran at 20℃; for 6h; | General Procedure: Methylation of Phenytoin (1a) Using tBuOK (Table 1, run 8) General procedure: To a solution of phenytoin (1a, 100 mg, 0.40 mmol) in THF (2.0 mL), tBuOK (Aldrich, 1 M solution in THF, 0.80 mL, 0.80 mmol) was added at r.t. After 3 min, CH3I (30 µL, 0.48 mmol) in THF (0.1 mL) was added at r.t. and the mixture was stirred at r.t. for 5 min. One molar HCl (2 mL) was added and the whole was extracted with AcOEt (2×10, 1×5 mL). The combined organic layer was washed with brine (1×5 mL) and dried over Na2SO4. The solvent was evaporated in vacuo, and the crude product was purified by column chromatography (n-hexane-AcOEt 2 : 1) to give 4a as colorless solids (83 mg, 79%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 55% 2: 5% | Stage #1: phenythoin With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 0.05h; Stage #2: ethyl bromoacetate In tetrahydrofuran at 20℃; for 2h; | General Procedure: Methylation of Phenytoin (1a) Using tBuOK (Table 1, run 8) General procedure: To a solution of phenytoin (1a, 100 mg, 0.40 mmol) in THF (2.0 mL), tBuOK (Aldrich, 1 M solution in THF, 0.80 mL, 0.80 mmol) was added at r.t. After 3 min, CH3I (30 µL, 0.48 mmol) in THF (0.1 mL) was added at r.t. and the mixture was stirred at r.t. for 5 min. One molar HCl (2 mL) was added and the whole was extracted with AcOEt (2×10, 1×5 mL). The combined organic layer was washed with brine (1×5 mL) and dried over Na2SO4. The solvent was evaporated in vacuo, and the crude product was purified by column chromatography (n-hexane-AcOEt 2 : 1) to give 4a as colorless solids (83 mg, 79%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tetrabutylammomium bromide In N,N-dimethyl-formamide for 2h; Reflux; Alkaline conditions; | 4.1.1. General procedure for the synthesis of 5,5-diphenylimidazolidin-2,4-diones derivative To a solution of the Phenytoin (2.5 g, 0.01 mol) in absoluteDMF (20 mL) and in presence of 1.3 equivalent of sodiumbicarbonate (1 g, 0.013 mol) the 1-bromodecane (3.2 mL,0.015 mol) was added and the reaction mixture was heatedunder reflux for 2 h. The solvent was concentrated underreduced pressure then diluted with ice-cold water (25 mL).The precipitated solid product was filtered than crystallizedfrom absolute ethanol; yield 89%; mp 65.2-65.3 C; IR(KBr)(cm1): 3400-3282 (N-H), 3059 (C-H aromatic), 2920,2865 (C-H aliphatic), 1774, 1716-1665 (CO); 1HNMR(300 MHz, DMSO-d6) d: 0.835 (t, 3H, CH3), 3.411 (t, 2H, CH2-N), 1.520-1.160(m, 16H, CH2) ; 7.343 (m, 10H, Ar-H), 9.583 (s,H, NH), |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With pyridine; copper(II) bis(trifluoromethanesulfonate) In ethanol at 25℃; for 24h; |
Tags: 57-41-0 synthesis path| 57-41-0 SDS| 57-41-0 COA| 57-41-0 purity| 57-41-0 application| 57-41-0 NMR| 57-41-0 COA| 57-41-0 structure
A228712[ 630-93-3 ]
Sodium 2,4-dioxo-5,5-diphenylimidazolidin-1-ide
Reason: Free-Salt
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
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 |
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.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :