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. : | 459-05-2 | MDL No. : | MFCD00041180 |
Formula : | C7H7FN2S | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | BRWKXKNZRVALNZ-UHFFFAOYSA-N |
M.W : | 170.21 | Pubchem ID : | 693061 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.0 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 46.2 |
TPSA : | 70.14 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.17 cm/s |
Log Po/w (iLOGP) : | 1.62 |
Log Po/w (XLOGP3) : | 1.64 |
Log Po/w (WLOGP) : | 1.71 |
Log Po/w (MLOGP) : | 1.63 |
Log Po/w (SILICOS-IT) : | 2.08 |
Consensus Log Po/w : | 1.74 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.2 |
Solubility : | 1.07 mg/ml ; 0.00631 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.73 |
Solubility : | 0.32 mg/ml ; 0.00188 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.52 |
Solubility : | 0.52 mg/ml ; 0.00305 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.45 |
Signal Word: | Danger | Class: | 6.1 |
Precautionary Statements: | P301+P310-P305+P351+P338 | UN#: | 2811 |
Hazard Statements: | H301-H319 | Packing Group: | Ⅲ |
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 |
---|---|---|
42% | With bromine In chloroform for 2h; | |
With chloroform; bromine | ||
With sulfuryl dichloride; bromine; chlorobenzene |
With bromine In chloroform | ||
With bromine In chloroform for 4h; Heating; | ||
With bromine In chloroform | ||
Multi-step reaction with 2 steps 1: bromine / chloroform / 4 h 2: ammonia / ethanol | ||
With bromine Reflux; | ||
With bromine; acetic acid; lithium bromide at 40℃; | ||
With sulfuryl dichloride; bromine; chlorobenzene | ||
With bromine In chloroform | ||
With bromine at 0 - 5℃; | ||
With bromine In dichloromethane at 5℃; | General procedure: Substituted phenylthiourea (0.1 mol) was taken in CHCl3 and stirred with a mechanical stirrer and bromine (0.1 mol) was added drop by drop for a period of an hour with continuous stirring. The temperature was maintained <5°C. After bromine addition, the stirring was maintained for 4-5 hours. The product obtained was dried, followed by SO2 water treatment and filtered. The filtrate obtained was treated with aq. NH3 in neutral conditions. The obtained precipitate was filtered, dried, and recrystallized from absolute alcohol. | |
With bromine In chloroform at 70℃; for 9h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium hydroxide In water | |
94.2% | With sodium hydroxide In water at 80℃; | 5.2 Step 2: Preparation of 1-(4-fluorophenyl)-thiourea i.e. compound 3b The 65.0g 2b was added to 700ml 10% sodium hydroxide solution, heated to 80 , stirring until the reaction was complete by TLC.The reaction solution was poured into 140ml of concentrated hydrochloric acid containing 1200g of ice and stirred at pH 8-9 with concentrated aqueous ammonia, stirred until the ice melted after filtering, the filtrate was discarded, the filter cake was washed with de-ionized water, and dried in vacuo under reduced pressure, and then the product was dried with acetone / petroleum ether 1: 3 recrystallized to give 38.0 g of off-white product, 94.2% yield. |
92% | Stage #1: N-((4-fluorophenyl)carbamothioyl)benzamide With water; sodium hydroxide at 100℃; for 1h; Stage #2: With hydrogenchloride In water | 37 l-(4-fluorophenyl)thiourea (C)The N-(4-fluorophenylcarbamothioyl)benzamide (2.74 g) was refluxed in 10% NaOH aqueous solution (40 mL) at 100°C for 1 hr. The reaction mixture was cooled and acidified with dilute HCl to get solid which was filtered and washed with water and dried. The dried solid was further recrystalized in dry ether to yield pure solid (92% yield). MS: m z 1751 (M + 1)+. |
80% | With sodium hydroxide at 80 - 85℃; for 0.15h; | |
70% | With sodium hydroxide at 100℃; | |
With sodium hydroxide | ||
With water; sodium hydroxide at 100℃; for 1h; Reflux; | General procedure D for Synthesis of 1-(4-fluorophenyl)thiourea analogues 10a-c General procedure: The N-(4-fluorophenylcarbamothioyl)benzamide was refluxed in 10% NaOH aqueous solution at 100 °C for 1 hr. The reaction mixture was cooled and acidified with dilute HCl to get solid which was filtered and washed with water and dried. The dried solid was further recrystallized in dry ether to yield pure solid. | |
With sodium hydroxide In water at 90℃; for 0.333333h; | ||
With water; sodium hydroxide Heating; | ||
With sodium hydroxide at 80 - 90℃; for 3h; | ||
With sodium hydroxide In water at 100℃; for 1h; | 3 General procedure: A solution of 1.00 g (3.33 mmol) N-(benzo[d][1,3]dioxol-5-ylcarbamothioyl)benzamide (D, Scheme 2 ) in 5 ml aqueous sodium hydroxide (2 M) was heated to 100 °C for 1 h. The precipitating solid, 1-(benzo[d][1,3]dioxol-5-yl)thiourea (E, Scheme 2 ), was collected and washed with H2O, yield: 529 mg (81%). | |
With ammonium hydroxide In methanol Reflux; | ||
With water; sodium hydroxide In ethanol for 2h; Reflux; | ||
With sodium hydroxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With ammonium hydroxide In water; acetonitrile at 20℃; for 3h; | Intermediate thioureas synthesis General procedure: To a solution of a (substituted)-phenylisothiocyanate derivative (0.6 M) in MeCN was added aqueous ammonia (25%, 1.5 eq). The solution was stirred at room temperature for 3 h. The reaction mixture was then concentrated. Purification was done by precipitation from a mixture of n-hexane/ethyl acetate mixture (3/2). The pure product was recovered as a powder after filtration in a quantitative yield. |
With ethanol; ammonia | ||
With ammonia In ethanol Yield given; |
With ammonia In N,N-dimethyl-formamide at 20℃; for 1h; | General Procedure for the synthesis of 4-Fluoro Phenyl thiourea To a stirred solution of DMF (4-5 ml), 4-Fluoro aniline (2 mmol, 254 mg) was added in slowly and followed by carbon disulphide (20 mmol (10 eq), 1520 mg) and sodium bicarbonate (2 mmol (1 eq), 168 mg) were added at room temperature. The whole reaction mixture stirred for one hour (until get the yellow color solid) at room temperature. Thiocarbomate formation was monitored by TLC. To this, CoSO4xH2O (25 mol%, 121 mg) and sodium bicarbonate (2 mmol (1 eq), 168 mg) were added slowly for 5 min and the reaction mixture stirred for 1 h. During this period, a block color precipitate was observed and settles at bottom of round bottom flask. The progress of the reaction was investigated by TLC (5% ethylacetate in hexane). After 1 h, ammonia solution (2 ml) was added slowly. Then the whole reaction mixture stirred for 1 h at room temperature. After finish the reaction, the reaction mixture was transferred into centrifuged tubes and the mixture was centrifuged for 10 min by using centrifugation machine. Block color solid was settled in the bottom of centrifuged tubes. The clear solution was concentrated by using rotary evaporator and the crude mixture was purified by silica gel (60-120 mesh) column chromatography using 20% Ethylacetate in Hexane as eluent to afford a 4-Fluoro phenyl thiourea as white solid. | |
With ammonium hydroxide In N,N-dimethyl-formamide at 20℃; for 1h; | Synthesis of cyanamides 2a-h,l-n (General method). General procedure: Aryl/alkyl isothiocyanate 1a-h,l-n (2 mmol) was addedslowly to stirred DMF (4-5 ml), followed by addition ofaqueous NH3 (2 ml, 2 mmol) at room temperature. Thereaction mixture was stirred for 1 h at room temperature.Thiourea formation was monitored by TLC on silica gel.Then CoSO4·H2O (121 mg, 0.5 mmol, 25 mol %) wasadded slowly followed by addition of NaOAc (164 mg,2 mmol), and the reaction mixture was stirred for 2 h atroom temperature. During this time, black precipitate(CoS) appeared and was removed by centrifugation. Theclear solution was concentrated using rotary evaporator,and the crude mixture was purified by columnchromatography using 10% EtOAc in hexane as eluent toobtain a corresponding cyanamide as a target product. | |
With ammonium hydroxide In dimethyl sulfoxide at 20℃; for 3h; | 2.2 General procedure for the preparationof arylcyanamide General procedure: To a stirred solution of DMSO (4-5 mL), respectiveisothiocyanate (2 mmol) was added slowly at roomtemperature and stirring further continued for 3 h atroom temperature. The progress of the reaction wasinvestigated by TLC (20% ethylacetate in hexane).After forming the respective substituted thiourea (asper TLC) Fe2(SO4)3.H2O (50 mol %, 417 mg) andNaOAc (2 mmol, 164 mg) were added to that solutionat room temperature, then the reaction mixture wasstirred for 2 h. During this time black color precipitate(FeS) was observed. And it was removed by centrifugation. The clear solution was concentrated byusing a rotary evaporator and the crude mixture waspurified by silica gel (60-120 mesh) column chromatographyusing Ethylacetate in Hexane as eluent toobtain a phenyl cyanamide as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59.9% | Stage #1: ammonium thiocyanate; 4-fluoroaniline With hydrogenchloride In water for 1h; Heating; Stage #2: Heating; | General procedure for the synthesis of aryl thiourea(1a-i) General procedure: To a suspension of (0.30 mol) of aryl amine in 100 mL ofwarm water, concentrated hydrochloric acid (HCl) (0.33mol, 9.16 mL) was added with stirring. The resulting solutionwas placed in a large porcelain evaporating dish,ammonium thiocyanate (0.3 mol, 8.33 g) was added and themixture was heated on a steam bath for 1 h. The liquid, fromwhich a mass of large needles of aryl amine thiocyanateseparated, was allowed to cool, set aside at room temperaturefor 1 h and then evaporated slowly to dryness over aperiod of 2-3 hrs. The crystalline residue was crushedfinely, 100 mL water was added, and again the mixture wasevaporated slowly. The dry grayish white residual powderwas heated finally on a steam bath for 4-5 hrs. The resultingmixture of crude substituted phenylthiourea and ammoniumchloride was powdered finely and suspended in 100 mL ofwater. The mixture was warmed slowly to 70 °C with stirring,and then allowed to cool to 35 °C and the solid wasfiltered with suction. The crude material was dissolved inabsolute ethanol, the solution boiled with decolourizingcarbon for a few minutes and then filtered. The whitecrystalline mass of substituted phenylthiourea, whichseparated on cooling and standing, was separated by filtration,was washed with light petroleum ether and dried.Thin layer chromatography was carried out on precoatedsilica plates, using the solvent system methanol: chloroform (1:9). Physical and spectral analysis confirmed the formationof the corresponding thiourea (Rabjohn, 2005). |
With hydrogenchloride | ||
With hydrogenchloride In water for 2h; Heating; |
With hydrogenchloride Heating; | ||
With hydrogenchloride In water Heating; | ||
With hydrogenchloride In water | ||
With hydrogenchloride In water Heating; | ||
With hydrogenchloride | ||
With hydrogenchloride In water Heating; | 3.2.1. General Procedure for Synthesis of Aryl Thioureas(2) General procedure: A mixture of concentrated hydrochloric acid (25 mL) andsubstituted anilines (1) (25 mL) in a conical flask was warmed gently. A freshly prepared saturated solution of ammonium thiocyanate in water (30 g in 60 mL) was added to above solution. The resultant solution was boiled until it got turbid. The turbid solution was then poured onto ice coldwater. Aryl thioure as (2) were separated as precipitates,filtered and crystallized from aqueous ethanol (80%) [33]. | |
With hydrogenchloride | ||
With hydrogenchloride Heating; | ||
Stage #1: 4-fluoroaniline With hydrogenchloride In water Reflux; Stage #2: ammonium thiocyanate In water Reflux; | 3.1.1. Synthesis of Substituted 2-aminobenzothiazole (3a-3g) General procedure: 0.1 mol of substituted aniline, concentrated HCl (9 mL), and H2O (25 mL) were refluxed for about 30-40 minutes. Then, it was cooled and 0.1 mol of ammonium thiocyanate was added and it was further refluxed for 4-5 hours and the product formation was confirmed by two-layer separation. After cooling, it was poured into a beaker containing ice. The solid phenylthiourea separated out was filtered, dried, and crystallized from absolute alcohol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With potassium hydroxide In ethanol for 24h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With potassium hydroxide In ethanol reflux, 12 h, RT. 24 h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With potassium hydroxide In ethanol for 24h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium hydroxide In ethanol for 24h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With sodium molybdate; dihydrogen peroxide; sodium chloride In water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With dihydrogen peroxide In water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | at 100℃; for 1h; | |
71% | In methanol at 20℃; | 4.3.2.3. Synthesis and characterization of substituted N'-carbamothioyl-N,N-dimethylformimidamide (6a-e) General procedure: 4.3.2.3.1. N'-carbamothioyl-N,N-dimethylformimidamide(6a). Thiourea 5a (1.0 eq) in methanol was reacted with 1,1-dimethoxy-N,N-dimethylmethanamine (2.0 eq) at room temperature for 3 h to get N'-carbamothioyl-N,N-dimethylformimidamide 6a. After completion of reaction, methanol was evaporated in vacuo to get compound 6a. 6a was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.6% | In ethanol Reflux; | 5.3 Step 3: S-methyl-N-(4-chlorophenyl)amidino thioether i.e. compound 4b The 43.0 g 3b and 53.8g CH3I was suspended in 500ml of anhydrous EtOH and warmed to reflux until TLC indicated the reaction was complete.EtOH was removed and concentrated to give a solid product, product was washed with ethyl acetate and concentrated to give an off-white solid product was 44.0 g, yield 96.6%. |
76% | In methanol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol at 25℃; for 16h; | 4.A A. l-(4-Fluoro-phenyI)-2-methyI-isothiourea (Cpd. 4b). To a solution of (4- Fluoro-phenyl)-thiourea (18.7 mg, 0.11 mmol) and methanol (0.25 niL) was added iodomethane (8 DL, 0.13 mmol). The mixture was stirred at 25°C for 16 h, then concentrated to a residue to provide crude compound 4b. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | In methanol at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 43% 2: 13% | With sodium hydroxide In water at 90℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With sodium hydroxide In water; acetone at 85 - 90℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: acetone / 2 h / 20 °C 2: 43 percent / NaOH / H2O / 20 h / 90 °C | ||
Multi-step reaction with 2 steps 1: 82 percent / benzene 2: 70 percent / 2,5 N NaOH / 100 °C | ||
Multi-step reaction with 2 steps 1: chloroform; water 2: ethanol; ammonia |
Multi-step reaction with 2 steps 1: benzene / 20 °C 2: water; sodium hydroxide / 1 h / 100 °C / Reflux | ||
Multi-step reaction with 2 steps 1: benzene / 2 h / 20 °C 2: sodium hydroxide / water / 0.33 h / 90 °C | ||
Multi-step reaction with 2 steps 1: benzene / 20 - 32 °C 2: sodium hydroxide; water / 1 h / 100 °C | ||
Multi-step reaction with 2 steps 1: hydrogenchloride / water / 0.5 h / Heating 2: water / Reflux | ||
Multi-step reaction with 2 steps 1: ethanol / 40 °C 2: water; sodium hydroxide / Heating | ||
Multi-step reaction with 2 steps 1: acetonitrile / 0.17 h / Milling; Green chemistry 2: ammonium chloride; sodium carbonate / neat (no solvent) / 1 h / Milling; Green chemistry | ||
Multi-step reaction with 2 steps 1: acetone / Reflux 2: ammonium hydroxide / methanol / Reflux | ||
Multi-step reaction with 2 steps 1.1: sodium hydrogencarbonate / N,N-dimethyl-formamide / 1 h / 20 °C 1.2: 1 h / 20 °C 2.1: ammonia / N,N-dimethyl-formamide / 1 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: acetone / 0.25 h / Reflux 1.2: 20 °C 2.1: sodium hydroxide / water / 80 °C | ||
Multi-step reaction with 2 steps 1: benzene 2: sodium hydroxide / water | ||
Multi-step reaction with 2 steps 1: benzene 2: sodium hydroxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In ethanol Reflux; | |
80% | With sodium carbonate In neat (no solvent) Milling; | General procedure: General procedure for the preparation of ethyl 2-methylthiazole-4-carboxylate (12a) An oily mixture of ethyl α-bromopyruvate (9, 2.14 g, 11 mmol) and thioacetamide (10a, 0.75 g, 10 mmol) was ground in presence of Na2CO3 (0.50 g) for 5-6 min. When it becomes solid, the progress of reaction was monitored with TLC. On completion of the reaction, water (20 ml) was added to the reaction followed by extraction with chloroform (20 ml). The organic layer thus separated was dried over anhy. Na2SO4. Excess of solvent was removed by distillation. Filtered the crude product and crystallized from aqueous ethanol (83%) to give pure solid 12a. Similarly, 12b-12g and 13a-13g were prepared following the above procedure and their formation was confirmed by comparing their melting points with literature values. |
In ethanol at 65℃; | B; 9 Protocol B:Ethyl bromopyruvate (6 mmol) was added to a solution of the thiourea (5 mmol) in ethanol (12 ml). The mixture was stirred overnight at 65°C. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure.The ester (10 mmol) was dissolved in ethanol (1.5 ml) and 2N NaOH (10 ml) was added. The reaction mixture was stirred overnight at 65°C. The reaction mixture was cooled to room temperature and ethanol was removed under reduced pressure. The residue was diluted with water (20 ml) and was extracted with EtOAc (2x20 ml). The water layer was cooled to 0°C and acidified with concentrated HCI. The precipitate was filtered, washed with water (3x10 ml) and dried under reduced pressure. |
In ethanol at 65℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | With pyridine In ethanol at 80℃; for 2h; | 1 Step 1: ethyl 2-[(4-fluorophenyl)amino]-4-methyl-i ,3-thiazole-5-carboxylate To a solution of 5.0 g (29 mmol) i-(4-fluorophenyl)thiourea (CAS-No [459-05-2], commercially available e.g. ABCR, Aldrich) and 4.8 g (29 mmol) ethyl 2-chloro-3- oxobutanoate in 100 mL ethanol was added 2.85 mL pyridine. Then this solution was heated to 80°C for 2 hours. After cooling to room temperature the mixture wasconcentrated under reduced pressure. To the residue was added 150 mL diethyl ether. After filtration the filtrate was washed with 150 mL water and 50 mL brine, then dried over sodium sulfate, filtered and concentrated under reduced pressure and dried to give 2.27 g (25% yield) of the desired title compound.1H NMR (400 MHz, DM50 d6): 6 (ppm) = 1.25 (t, 3H), 2.50 (s, 3H), 4.19 (q, 2H), 7.16 -7.21 (m, 2H), 7.58 - 7.64 (m, 2H), 10.65 (s, 1H). |
In ethanol at 65℃; | A; 1 Protocol A: Ethyl^-chloroaceto-acetate (1.2 eq, 12 mmol) was added to a solution of the thiourea (10 mmol) in ethanol (20 ml). The mixture was stirred overnight at 65°C. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The ester (10 mmol) was dissolved in ethanol (4 ml) and 2N NaOH (20 ml) was added. The reaction mixture was stirred overnight at 65°C. The reaction mixture was cooled to room temperature and ethanol was removed under reduced pressure. The residue was diluted with water (20 ml) and was extracted with EtOAc (2x20 ml). The water layer was cooled to 0°C and acidified with concentrated HCI. The precipitate was filtered, washed with water (3x10 ml) and dried under reduced pressure |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol at 25℃; for 16h; | 4.A To a solution of (4-Fluoro-phenyl)-thiourea (18.7 mg, 0.11 mmol) and methanol (0.25 mL) was added iodomethane (8 μl_, 0.13 mmol). The mixture was stirred at 25°C for 16 h, then concentrated to a residue to provide crude compound 4b. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol | 57 Ethyl 2-p-fluoroanilinothiazole-4-carboxylate PREPARATION 57 Ethyl 2-p-fluoroanilinothiazole-4-carboxylate The reaction described in Preparation 42 was repeated, but using 12 g of p-fluorophenylthiourea, 14.8 g of ethyl bromopyruvate, and 120 ml of ethanol, giving the title compound as pale yellow prisms. Melting Point: 133° to 136° C. Nuclear Magnetic Resonance Spectrum (hexadeuterated acetone) δ ppm: 1.34 (3H, triplet. J=7 Hz), 4.31 (2H, quartet, J=7 Hz), 7.10 (2H, triplet, J=9 Hz), 7.65 (1H, singlet), 7.78 (2H, doublet of doublets, J=9 and 5 Hz), 9.2.-9.6 (1H, broad). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With sodium hydroxide In acetone for 3h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With dihydrogen peroxide | |
74.9% | With dihydrogen peroxide; sodium hydroxide In water at 0℃; for 3h; | General procedure for the synthesis of (5-imino-4-phenyl-4,5-dihydro-[1,2,4] thiadiazol-3-yl)-phenyl-aminederivatives (2a-i) General procedure: The substituted phenylthiourea (4.18 × 10-3 mol) wascompletely dissolved in aqueous sodium hydroxide (2N, 30mL, 4 × 10-2 mol) at 0 °C. Hydrogen peroxide (30 %, 0.13mL, 5.51 × 10-3 mol) was then added drop-wise to thereaction mixture. The mixture was stirred for 3 hrs. at thesame temperature and then it was acidified with concentratedHCl to get a pH of 4.5. The resulting colourlesssolid was separated and collected by filtration. It wasrecrystallized from ethanol to give the pure compound (Choet al., 1991). TLC was carried out on precoated silica plateusing the slovent system, methanol: chloroform (1:9). |
With hydrogenchloride; water; dihydrogen peroxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | Stage #1: (4-fluoro-phenyl)-thiourea; 1,3-Dichloroacetone In N,N-dimethyl-formamide for 1h; Heating / reflux; Stage #2: 2-amino-4-{4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]phenyl}-6-mercaptopyridine-3,5-dicarbonitrile With sodium hydrogencarbonate In N,N-dimethyl-formamide at 20℃; for 16h; | 5A Example 5A 2-Amino-4-{4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]phenyl}-6-[({2-[(4-fluorophenyl)amino]-1,3-thiazol-4-yl}methyl)thio]pyridine-3,5-dicarbonitrile 102 mg (0.6 mmol) of 4-fluorophenylthiourea and 73.6 mg (0.58 mmol) of 1,3-dichloroacetone are dissolved in 2.5 ml of ethanol, and the mixture is stirred under reflux for 60 min. The mixture is allowed to cool and concentrated using a rotary evaporator. The residue is taken up in 1.5 ml of DMF, 153 mg (0.4 mmol) of the compound from Example 3A and 101 mg (1.2 mmol) of sodium bicarbonate are added and the reaction solution is stirred at RT for a further 16 h. The reaction mixture is purified directly by preparative HPLC chromatography (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5). Yield: 62 mg (26% of theory) 1H-NMR (400 MHz, DMSO-d6): δ=10.24 (s, 1H), 8.08 (br. s, 2H), 7.62 (dd, 2H), 7.47 (d, 2H), 7.13 (m, 4H), 6.97 (s, 1H), 4.49-4.39 (m, 3H), 4.10 (m, 3H), 3.78 (dd, 1H), 1.36 (s, 3H), 1.31 (s, 3H). |
26% | Stage #1: (4-fluoro-phenyl)-thiourea; 1,3-Dichloroacetone In ethanol for 1h; Reflux; Stage #2: 2-amino-4-{4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]phenyl}-6-mercaptopyridine-3,5-dicarbonitrile With sodium hydrogencarbonate In N,N-dimethyl-formamide at 20℃; for 16h; | 5A 102 mg (0.6 mmol) of 4-fluorophenylthiourea and 73.6 mg (0.58 mmol) of 1,3-dichloroacetone are dissolved in 2.5 ml of ethanol, and the mixture is stirred under reflux for 60 min. The mixture is allowed to cool and concentrated on a rotary evaporator. The residue is taken up in 1.5 ml of DMF, 153 mg (0.4 mmol) of the compound from Example 3A and 101 mg (1.2 mmol) of sodium bicarbonate are added and the reaction solution is stirred at RT for a further 16 h. The reaction mixture is directly purified chromatographically by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5).Yield: 62 mg (26% of theory)1H-NMR (400 MHz, DMSO-d6): δ=10.24 (s, 1H), 8.08 (br. s, 2H), 7.62 (dd, 2H), 7.47 (d, 2H), 7.13 (m, 4H), 6.97 (s, 1H), 4.49-4.39 (m, 3H), 4.10 (m, 3H), 3.78 (dd, 1H), 1.36 (s, 3H), 1.31 (s, 3H).LC-MS (method 2): Rt=2.51 min; MS (ESIpos): m/z=589 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | Stage #1: (4-fluoro-phenyl)-thiourea; 1,3-Dichloroacetone In ethanol at 85℃; for 1h; Stage #2: 2-amino-4-[4-(2-azidoethoxy)phenyl]-6-mercaptopyridine-3,5-dicarbonitrile With sodium hydrogencarbonate In N,N-dimethyl-formamide at 20℃; for 20h; | 39A Example 39A 2-Amino-4-[4-(2-azidoethoxy)phenyl]-6-[({2-[(4-fluorophenyl)amino]-1,3-thiazol-4-yl}methyl)thio]pyridine-3,5-dicarbonitrile A solution of 74 mg (0.44 mmol) of 4-fluorophenylthiourea and 55 mg (0.44 mmol) of 1,3-dichloroacetone in 5 ml of ethanol is stirred at +85° C. for 60 min. After removal of the solvent on a rotary evaporator, the residue is taken up in 5 ml of DMF, 105 mg (0.31 mmol) of the compound from Example 38A and 78 mg (0.93 mmol) of sodium bicarbonate are added and the mixture is then stirred at RT for 20 h. The mixture is then added to 15 ml of saturated sodium bicarbonate solution. The mixture is extracted with ethyl acetate (three times, 15 ml each) and the combined organic phases are dried over magnesium sulphate. After removal of the solvent on a rotary evaporator, the crude product is purified chromatographically on silica gel 60 (mobile phase gradient dichloromethane/ethanol 200:1→20:1). Yield: 79 mg (47% of theory) 1H-NMR (400 MHz, DMSO-d6): δ=10.22 (s, 1H), 8.27-7.86 (br. s, 2H), 7.66-7.58 (m, 2H), 7.50 (d, 2H), 7.17-7.08 (m, 4H), 6.96 (s, 1H), 4.46 (s, 2H), 4.31-4.22 (m, 2H), 3.74-3.67 (m, 2H). |
47% | Stage #1: (4-fluoro-phenyl)-thiourea; 1,3-Dichloroacetone In ethanol at 85℃; for 1h; Stage #2: 2-amino-4-[4-(2-azidoethoxy)phenyl]-6-mercaptopyridine-3,5-dicarbonitrile With sodium hydrogencarbonate In N,N-dimethyl-formamide at 20℃; for 20h; | 39A A solution of 74 mg (0.44 mmol) 4-fluorophenylthiourea and 55 mg (0.44 mmol) 1,3-dichloro-acetone in 5 ml ethanol is stirred at +85° C. for 60 min. After removal of the solvent on a rotary evaporator, the residue is taken up in 5 ml of DMF, 105 mg (0.31 mmol) of the compound from example 38A and 78 mg (0.93 mmol) of sodium bicarbonate are added and the mixture is then stirred at RT for 20 h. The mixture is then added to 15 ml of saturated sodium bicarbonate solution. The mixture is extracted with ethyl acetate (three times 15 ml each), and the combined organic phases are dried over magnesium sulfate. After removal of the solvent on a rotary evaporator, the crude product is purified chromatographically on silica gel 60 (mobile phase gradient dichloromethane/ethanol 200:1→20:1).Yield: 79 mg (47% of theory)1H-NMR (400 MHz, DMSO-d6): δ=10.22 (s, 1H), 8.27-7.86 (br. s, 2H), 7.66-7.58 (m, 2H), 7.50 d, 2H), 7.17-7.08 (m, 4H), 6.96 (s, 1H), 4.46 (s, 2H), 4.31-4.22 (m, 2H), 3.74-3.67 (m, 2H).LC-MS (method 2): Rt=2.72 min; MS (ESIpos): m/z=544 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | Stage #1: (4-fluoro-phenyl)-thiourea; 1,3-Dichloroacetone In N,N-dimethyl-formamide at 80℃; for 3h; Stage #2: 2-amino-4-[4-(2-[tert-butyl(dimethyl)silyl]oxy}propoxy)phenyl]-6-mercaptopyridine-3,5-dicarbonitrile In N,N-dimethyl-formamide at 20℃; for 20h; | 43A Example 43A 2-Amino-4-[4-(2-[tert-butyl(dimethyl)silyl]oxy}propoxy)phenyl]-6-[({2-[(4-fluorophenyl)amino]-1,3-thiazol-4-yl}methyl)thio]pyridine-3,5-dicarbonitrile A solution of 78.6 mg (0.46 mmol) of 4-fluorophenylthiourea and 56.0 mg (0.44 mmol) of 1,3-dichloroacetone in 2 ml of dry DMF is stirred at +80° C. for 3 h. After cooling to RT, 370 mg (0.42 mmol) of the compound from Example 42A are added, and the mixture is then stirred at RT for 20 h. The reaction mixture is purified directly by two preparative HPLCs (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5). Yield: 0.44 g (14% of theory) 1H-NMR (400 MHz, DMSO-d6): δ=10.21 (s, 1H), 8.18-7.93 (br. s, 2H), 7.60 (dd, 2H), 7.47 (d, 2H), 7.12 (t, 2H), 7.07 (d, 2H), 6.95 (s, 1H), 4.44 (s, 2H), 4.21-4.12 (m, 1H), 3.96 (dd, 1H), 3.87 (dd, 1H), 1.18 (d, 3H), 0.87 (s, 9H), 0.08 (d, 6H). |
14% | Stage #1: (4-fluoro-phenyl)-thiourea; 1,3-Dichloroacetone In N,N-dimethyl-formamide at 80℃; for 3h; Stage #2: 2-amino-4-[4-(2-[tert-butyl(dimethyl)silyl]oxy}propoxy)phenyl]-6-mercaptopyridine-3,5-dicarbonitrile In N,N-dimethyl-formamide at 20℃; for 20h; | 43A A solution of 78.6 mg (0.46 mmol) of 4-fluorophenylthiourea and 56.0 mg (0.44 mmol) of 1,3-dichloroacetone in 2 ml of dry DMF is stirred at +80° C. for 3 h. After cooling to RT, 370 mg (0.42 mmol) of the compound from example 42A are added, and the mixture is then stirred at RT for 20 h. The reaction mixture is purified directly twice by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5).Yield: 0.44 g (14% of theory)1H-NMR (400 MHz, DMSO-d6): δ=10.21 (s, 1H), 8.18-7.93 (br. s, 2H), 7.60 (dd, 2H), 7.47 (d, 2H), 7.12 (t, 2H), 7.07 (d, 2H), 6.95 (s, 1H), 4.44 (s, 2H), 4.21-4.12 (m, 1H), 3.96 (dd, 1H), 3.87 (dd, 1H), 1.18 (d, 3H), 0.87 (s, 9H), 0.08 (d, 6H).LC-MS (method 5): Rt=7.35 min; MS (ESIpos): m/z=647 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | Stage #1: (4-fluoro-phenyl)-thiourea; 1,3-Dichloroacetone In ethanol for 1h; Heating / reflux; Stage #2: 2-amino-4-[4-(2-hydroxyethoxy)phenyl]-6-sulfanylpyridine-3,5-dicarbonitrile With sodium hydrogencarbonate In N,N-dimethyl-formamide at 20℃; | 8 Example 8 2-Amino-6-[({2-[(4-fluorophenyl)amino]-1,3-thiazol-4-yl}methyl)thio]-4-[4-(2-hydroxyethoxy)-phenyl]pyridine-3,5-dicarbonitrile 244 mg (1.92 mmol) of 1,3-dichloroacetone are added to a solution of 327 mg (1.92 mmol) of 4-fluorophenylthiourea in 8 ml of ethanol, and the mixture is stirred under reflux for 1 h. The mixture is concentrated, the residue is dissolved in 4 ml of DMF, 429 mg (1.37 mmol) of 2-amino-4-[4-(2-hydroxyethoxy)phenyl]-6-mercaptopyridine-3,5-dicarbonitrile (preparation see WO 03/053441, Example 6/Method 1, Step 1) and 346 mg (4.1 mmol) of sodium bicarbonate are added and the mixture is stirred at RT overnight. After addition of water, the precipitate is decanted off and the residue is triturated with dichloromethane. After chromatography on silica gel (mobile phase dichloromethane/methanol 50:1), the title compound is obtained as a yellowish solid. Yield: 316 mg (44% of theory) HPLC (Method 1): Rt=4.24 min 1H-NMR (400 MHz, DMSO-d6): δ=10.23 (s, 1H), 8.1 (br. s, 2H), 7.62 (dd, 2H), 7.47 (d, 2H), 7.12 (dd, 4H), 6.96 (s, 1H), 4.92 (t, 1H), 4.45 (s, 2H), 4.07 (t, 2H), 3.74 (q, 2H). |
44% | Stage #1: (4-fluoro-phenyl)-thiourea; 1,3-Dichloroacetone In ethanol for 1h; Reflux; Stage #2: 2-amino-4-[4-(2-hydroxyethoxy)phenyl]-6-sulfanylpyridine-3,5-dicarbonitrile With sodium hydrogencarbonate In N,N-dimethyl-formamide at 20℃; | 8 244 mg (1.92 mmol) of 1,3-dichloroacetone are added to a solution of 327 mg (1.92 mmol) of 4-fluorophenylthiourea in 8 ml of ethanol, and the mixture is stirred under reflux for 1 h. The mixture is concentrated, the residue is dissolved in 4 ml of DMF, 429 mg (1.37 mmol) of 2-amino-4-[4-(2-hydroxyethoxy)phenyl]-6-mercaptopyridine-3,5-dicarbonitrile (preparation see WO 03/053441, example 6/method 1, 1st step) and 346 mg (4.1 mmol) of sodium bicarbonate are added and the mixture is stirred at RT overnight. After addition of water, the precipitate is decanted off and the residue is triturated with dichloromethane. Chromatography on silica gel (mobile phase dichloromethane/methanol 50:1) gives the title compound as a yellowish solid.Yield: 316 mg (44% of theory)HPLC (method 1): Rt=4.24 min1H-NMR (400 MHz, DMSO-d6): δ=10.23 (s, 1H), 8.1 (br. s, 2H), 7.62 (dd, 2H), 7.47 (d, 2H), 7.12 (dd, 4H), 6.96 (s, 1H), 4.92 (t, 1H), 4.45 (s, 2H), 4.07 (t, 2H), 3.74 (q, 2H).LC-MS (method 2): Rt=2.39 min; MS (ESIpos): m/z=519 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With hydrogenchloride In water for 1h; | 13 Both reagents were refluxed overnight in HCl 1N. The orange color of the aniline disappeared after 1 h. The mixture was cooled and the precipitate formed was collected by filtration and washed with water (30 mL). Yield 3 g (35%). |
With hydrogenchloride Heating; | ||
With hydrogenchloride at 80℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.3% | With sodium acetate In ethanol at 60℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Example 1-167V-(4-Fluor ophenyl)-4-(4-pyridinyl)- 1 ,3-thiazol-2-amine (33). [0249] A mixture of bromoketone hydrobromide 1 (0.83 g, 2.94 mmol) and 4- fluorophenylthiourea (32) (0.50 g, 2.94 mmol) in EtOH (20 mL) was stirred at reflux temperature for 2 h. The mixture was cooled to 20 0C, diluted with water (50 mL), the pH adjusted to ca. 8 with aqueous NH3 and the mixture stirred at 5 0C for 2 h. The precipitate was filtered, washed with water (5 mL) and dried. The crude solid was purified by column chromatography, eluting with a gradient (50-100%) of EtO Ac/pet, ether, to give amine 33 (0.76 g, 96%) as a cream powder: mp (EtOAc/pet. ether) 211-213 0C; 1H NMR delta 10.37 (br s, 1 H, NH), 8.61 (dd, J = 4.5, 1.6 Hz, 2 H, H-2', H-6'), 7.84 (dd, J= 4.5, 1.6 Hz, 2 H, H-3', H-5'), 7.73-7.78 (m, 2 H, H-3', H-5'), 7.70 (s, 1 H, H-5), 7.17-7.23 (m, 2 H, H-2", H-6"); 13C NMR delta 163.5, 156.9 (d, J= 241 Hz), 150.0 (2), 147.6, 140.9, 137.4, 119.8 (2), 118.4 (2, d, J= 7 Hz), 115.4 (2, d, J= 22 Hz), 107.3. Anal, calcd for Ci4Hi0FN3S: C, 61.98; H, 3.72; N, 15.49. Found: C, 62.14; H, 3.79; N, 15.49%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | Stage #1: (4-fluoro-phenyl)-thiourea; 1,3-Dichloroacetone In N,N-dimethyl-formamide at 80℃; for 3h; Stage #2: cis-2-amino-4-(4-[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-6-mercaptopyridine-3,5-dicarbonitrile With sodium hydrogencarbonate In N,N-dimethyl-formamide at 20℃; for 20h; | 16A Example 16A2-Amino-4-(cis-4-[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-6-[({2-[(4-fluorophenyl)amino]-1,3-thiazol-4-yl}methyl)thio]pyridine-3,5-dicarbonitrile; 43 mg (0.26 mmol) of 4-fluorophenylthiourea and 31 mg (0.24 mmol) of 1,3-dichloroacetone are dissolved in 2 ml DMF and stirred at +80° C. for 3 h. After cooling to RT 93 mg (0.23 mmol) of the compound from Example 12A (cis isomer) and 78 mg (0.93 mmol) of sodium bicarbonate are added, and the reaction mixture is stirred at RT for 20 h. The mixture is then directly purified by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5).Yield: 66 mg (43% of theory)1H-NMR (500 MHz, DMSO-d6): δ=10.22 (s, 1H), 8.05-7.87 (br. s, 2H), 7.63-7.56 (m, 2H), 7.12 (t, 2H), 6.92 (s, 1H), 4.40 (s, 2H), 4.05 (br. s, 1H), 2.91-2.82 (m, 1H), 2.48-1.68 (m, 2H), 1.58-1.47 (m, 2H), 1.47-1.39 (m, 2H), 0.89 (s, 9H), 0.06 (s, 6H).LC-MS (Method 13): Rt=3.49 min; MS (ESIpos): m/z=595 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sodium hydroxide In water; acetone at 85 - 90℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | In N,N-dimethyl-formamide at 80℃; for 4h; | 18.A.B Example 18A 4-(Chloromethyl)-N-(4-fluorophenyl)-1,3-thiazole-2-amine Method A: Over a period of 1.5 h, a warm solution of 160 g (1.26 mol) of 1,3-dichloroacetone in 480 ml of acetone is metered into a suspension von 202 g (1.19 mol) of 4-fluorophenylthiourea in 660 ml of acetone, and the mixture is stirred at 40° C. for 4.5 h and at RT overnight. The crystals are filtered off with suction, washed with acetone and dried under reduced pressure at 50° C. Yield: 328 g of colourless crystals (93% of theory) According to NMR, the product obtained consists to about 22% of the desired title compound in a mixture with about 78% of the non-dehydrated intermediate 4-(chloromethyl)-2-[(4-fluorophenyl)amino]-4,5-dihydro-1,3-thiazol-4-ol. This product is further used as such, without further separation. Method B: 600 mg (4.7 mmol) of 1,3-dichloroacetone and 768 mg (4.5 mmol) of 4-fluorophenylthiourea are dissolved in 10 ml of DMF and stirred at 80° C. for 4 h. 200 ml of water are added, and the mixture is extracted three times with ethyl acetate. The combined organic phases are washed with water and saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated to give a dark oil. |
In N,N-dimethyl-formamide at 80℃; for 3h; | 2 Example 2; 2'-Amino-6'-[({2-[(4-fluorophenyl)amino]-1,3-thiazol-4-yl}methyl)thio]-6-[(2-hydroxyethyl)amino]-3,4'-bipyridine-3',5'-dicarbonitrile; 18 mg (0.10 mmol) of 4-fluorophenylthiourea and 13 mg (0.10 mmol) of 1,3-dichloroacetone are dissolved in 2 ml of DMF, and the reaction solution is stirred at 80° C. for 3 h. After cooling, 89 mg (0.09 mmol, 33% pure) of the compound from example 4A and 32 mg (0.38 mmol) of sodium bicarbonate are added, and the mixture is stirred at RT for a further 20 h. The mixture is then filtered through a paper filter, and the filtrate is purified directly by preparative HPLC (column: YMC GEL ODS-AQ S-5/15 μm; mobile phase gradient: acetonitrile/water 10:90→95:5). Sat. sodium bicarbonate solution (5 ml) is added to the product fraction obtained, and the mixture is extracted with ethyl acetate (three times, 5 ml each). The combined organic phases are dried over magnesium sulphate, and the solvent is removed on a rotary evaporator.Yield: 18 mg (35% of theory)1H-NMR (300 MHz, DMSO-d6): δ=10.24 (s, 1H), 8.13 (d, 1H), 7.67-7.59 (m, 2H), 7.56 (dd, 1H), 7.27-7.19 (m, 1H), 7.19-7.09 (m, 2H), 6.96 (s, 1H), 6.61 (d, 1H), 4.77 (t, 1H), 4.44 (s, 2H), 3.59-3.51 (m, 2H), 3.49-3.35 (m, 2H).LC-MS (Method 3): Rt=1.83 min; MS (ESIpos): m/z=519 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: (4-fluoro-phenyl)-thiourea; para-bromophenacyl bromide In ethanol at 30 - 35℃; for 2.25h; Sonication; Stage #2: With ammonium hydroxide In ethanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | In tetrahydrofuran at 20℃; for 0.75h; | 28 N,4-bis(4-fluorophenyl)thiazol-2-amine (6)The reaction of l-(4-fluorophenyl)thiourea (340, 2mM) and freshly synthesized 2-bromo-l-(4- fluorophenyl)ethanone (435mg, 2mM) in anhydrous THF at room temperature for 45 mins resulted in the formation of suspension, which was filtered and dried to yield the final product (73% yield). mp 127°C. NMR (300 MHz, CDC13): δ (ppm) 11.82 (s, IH), 7.80 (m, IH), 7.60 (m, IH), 7.39 (m, 2H), 7.24 (m, 4H), 7.02 (m, IH), 6.62 (s, IH). IR (KBr) cm 1: 3211, 3114, 2942, 2366, 1660, 1056. MS: m/z 289 (M + 1)+. HRMS (ESI) m/z [M+l]+ calcd for ClsHi0F.N2S: 289.0533; found: 289.0491. |
With triethylamine In tetrahydrofuran at 20℃; for 0.5h; | General procedure E for the synthesis of substituted 4-phenylthiazol-2-yl derivatives 7a-d, 8a-c, 11, 12a-c, and 13a-d General procedure: The reaction of the equimolar amounts of the particular thiosemicarbazone and freshly synthesized substituted α-bromo-acetophenones in THF at room temperature for half-an-hour resulted in the formation of suspension, which was filtered and dried to yield the final product (1-4) in high yield. | |
at 80℃; Flow reactor; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol at 25℃; for 16h; | 4.A 1-(4-Fluoro-phenyl)-2-methyl-isothiourea (Cpd. 4b). To a solution of (4-Fluoro-phenyl)-thiourea (18.7 mg, 0.11 mmol) and methanol (0.25 mL) was added iodomethane (8 μL, 0.13 mmol). The mixture was stirred at 25° C. for 16 h, then concentrated to a residue to provide crude compound 4b. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With sodium hydroxide In acetone at 85 - 95℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water at 70℃; | General procedure: β-Cyclodextrin (10 mol %) was dissolved in water (15 ml) at 70 °C and phenylacetylene (1.0 mmol) was added followed by NBS. After 10 min, thiourea (1.0 mmol) was added to this reaction mixture and stirred at 70 °C until the reaction was complete (Table 1). The mixture was extracted with ethyl acetate, and the extract was filtered. The organic layer was washed with water and dried over anhydrous Na2SO4, the solvent was removed under reduced pressure, and the resulting crude product was further purified by column chromatography using hexane and EtOAc as eluent to give the title compound. The aqueous layer was cooled to 5 °C to recover β-CD by filtration. This β-CD was recycled without any loss of activity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water at 70℃; | General procedure: β-Cyclodextrin (10 mol %) was dissolved in water (15 ml) at 70 °C and phenylacetylene (1.0 mmol) was added followed by NBS. After 10 min, thiourea (1.0 mmol) was added to this reaction mixture and stirred at 70 °C until the reaction was complete (Table 1). The mixture was extracted with ethyl acetate, and the extract was filtered. The organic layer was washed with water and dried over anhydrous Na2SO4, the solvent was removed under reduced pressure, and the resulting crude product was further purified by column chromatography using hexane and EtOAc as eluent to give the title compound. The aqueous layer was cooled to 5 °C to recover β-CD by filtration. This β-CD was recycled without any loss of activity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | In tetrahydrofuran; at 32℃; for 1h; | N-(2,5-dimethoxyphenyl)-4-(4-fluorophenyl)thiazol-2-amine (7a)The reaction of the l-(4-fluorpphenyl)thiourea (340, 2mM) and freshly synthesized 2-bromo-l- (2,5-dimethoxyphenyl)ethanone (519mg, 2mM) in anhydrous THF at 32C for 60 mins resulted in the formation of suspension, which was filtered and dried to yield the final product (79% yield). mp 160C. l NMR (300 MHz, CDCI3): delta (ppm) 8.6 (s, IH), 8.16 (d, 2H, J = 9 Hz), 8.04 (d, IH, J = 2.7 Hz), 7.65 (s, IH), 7.62 (t, IH, J = 7.98 Hz, 15.99 Hz), 6.86 (d, IH, J = 9 Hz), 6.58 (d, IH, J = 2.88 Hz), 6.56 (d, IH, J = 0.9 Hz). IR (KBr) cm 1: 3507, 3076, 2938, 2366, 1578, 1022. MS: m/z 331 (M + 1)+. HRMS (ESI) m/z [M + 1]+ calcd for C 15H10F2N2S: 331.0838; found: 289.0829 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol for 17h; Reflux; | XXX Scheme XXX[105] 3- 2-(4-Fluoro-phenylamino)-thia2ol-4-yl -hexahvdro-pyrrolo[3,2-b]pyrrole- 1-carboxylic acid benzyl ester (31): A solution of 19 (1.46 g, 3.12 mmol) and 4-fluorophenyl thiourea (585 mg, 3.44 mmol) in EtOH (50 mL) was heated to reflux in a pre-heated oil bath. After 17 h, the reaction mixture was cooled to ambient temperature and concentrated. The residue was dissolved in DCM (10 mL), cooled to 0 °C, and treated with TFA (4 mL). After 5 h, the reaction mixture was concentrated. The residue was diluted with EtOAc, washed successively with aqueous NaHC03 (sat.), brine, dried over anhydrous Na- 2S04, filtered and concentrated to afford 31 (1.44 g, quant.) as a brown- colored foam. Mass spectrum, m/z [439.1] (M + H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With acetic acid Reflux; | 13 The reagents were stirred in acetic acid and heated to reflux resulting in a clear solution followed by precipitation formation. The mixture was refluxed for 3-5 hours (conversion of starting materials was monitored by HPLC). The mixture was cooled to rt, and the solid was collected by filtration, washed with ice water (80 mL), air dried and then vacuum dried. White powder, quantitative yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | General procedure: 5.1.1 General procedure A (for synthesis of compounds 1-19). To 2-bromoacetylpyridine hydrobromide (1.0 equiv) in anhydrous ethanol (5 mL) was added the corresponding thiourea (1.0 equiv, 0.2 g) and the reaction mixture refluxed for 4 h. After cooling to ambient temperature the reaction mixture was poured into water. The pH of the mixture was adjusted to pH 8 with concentrated aqueous NH4OH and the mixture stirred for 2 h. The precipitate was filtered, washed with ethanol and dried to afford the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | In ethanol at 70℃; | 4.3 General procedure for the synthesis of compounds 4a-n, 6-11, 15a, 6, 11-14, 17-19h (Hantzsch synthesis) General procedure: The properly substituted bromoacetophenone 4, 6-15, 17-19 (1 equiv) and thioureas a-n (1 equiv) were solubilized in dry ethanol (5mLmmol-1 of bromoacetophenone) and reacted at 70°C until consumption of the starting materials as indicated by TLC. After cooling, the solvent was evaporated and the residue obtained was washed with diethyl ether (3×10mL) to give the title compounds as a powder in good overall yields. In some cases, the crude material was purified by flash column chromatography. Yields, purification methods and purity are reported in details in the SI. Analytical data for compounds n, 6a, 8a, 15a, matched the data published previously [27,33,32,31]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In ethanol at 70℃; | 4.3 General procedure for the synthesis of compounds 4a-n, 6-11, 15a, 6, 11-14, 17-19h (Hantzsch synthesis) General procedure: The properly substituted bromoacetophenone 4, 6-15, 17-19 (1 equiv) and thioureas a-n (1 equiv) were solubilized in dry ethanol (5mLmmol-1 of bromoacetophenone) and reacted at 70°C until consumption of the starting materials as indicated by TLC. After cooling, the solvent was evaporated and the residue obtained was washed with diethyl ether (3×10mL) to give the title compounds as a powder in good overall yields. In some cases, the crude material was purified by flash column chromatography. Yields, purification methods and purity are reported in details in the SI. Analytical data for compounds n, 6a, 8a, 15a, matched the data published previously [27,33,32,31]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | In ethanol at 80℃; for 0.5h; Microwave irradiation; | 4 General procedure: A solution of 150 mg (0.64 mmol) 2-bromo-1-(4-chlorophenyl)-ethanone (B, Scheme 2 ) and 126 mg (0.64 mmol) 1-(benzo[d][1,3]dioxol-5-yl)thiourea (E, Scheme 2 ) in 2 ml ethanol was heated to 80 °C for 30 min under microwave irradiation. The precipitated white hydrobromide salt was collected, washed with H2O and cold ethanol, yield: 182 mg (69%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With hydrogenchloride In water for 2h; Reflux; | General procedure 1 General procedure: 2-Anilino thiazoles were prepared by acid catalyzed condensation of N-phenylthioureas and 2-chloro-1,1-dimethoxyethane. A mixture of N-phenylthiourea and 2-chloro-1,1-dimethoxyethanein 1:1 mol ratio and a few drops of concentrated HCl were dissolvedin water (100 ml). The reaction mixture was refluxed for 2 h. Cold water (100 mL) was added to the reaction mixture, followedby aqueous NaOH to make the solution alkaline (pH 8).The resulting precipitates were filtered on Buchner Funnel and washed with cold water. It was recrystallized from chloroform and hexane (3:1). |
With hydrogenchloride In water for 2h; Reflux; | Synthesis of N-arylthiazol-2-amine General procedure: A mixture of N-arylthiourea (0.357 mmol), 2-chloro-1,1-dimethoxyethane (0.338 mmol) and few drops of concentratedHCl were dissolved in water (50 mL), and the mixture was refluxed for 2 h. Cold water (50 mL) was added to it, followed by aqueous NaOH to make the solutionalkaline (pH 8). The resulting precipitates were filtered,washed with cold water and recrystallization was done using chloroform and hexane (ration 3:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | In methanol at 100℃; for 0.0833333h; Sealed tube; Microwave irradiation; | General Procedure for the Preparation of Fused Bicyclic2-Aminothiazolyl Compounds General procedure: To a microwave vial (2-5 mL) were added aryl thiourea 1 (1mmol), α,β-epoxy cycloketone 2 (1.05 mmol), and thecorresponding alcohol (2 mL). The sealed vial was heated inthe Biotage Initiator Synthesizer for an appropriate time. Themixture was then cooled to r.t., and the residue was obtainedafter evaporating under vacuum. The residue was subjectedto purification over silica gel chromatography eluting withPE-EtOAc (9:1, v/v) to afford target compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | In ethanol at 130℃; for 1h; Sealed tube; Microwave irradiation; | General Procedure for the Preparation of Fused Bicyclic2-Aminothiazolyl Compounds General procedure: To a microwave vial (2-5 mL) were added aryl thiourea 1 (1mmol), α,β-epoxy cycloketone 2 (1.05 mmol), and thecorresponding alcohol (2 mL). The sealed vial was heated inthe Biotage Initiator Synthesizer for an appropriate time. Themixture was then cooled to r.t., and the residue was obtainedafter evaporating under vacuum. The residue was subjectedto purification over silica gel chromatography eluting withPE-EtOAc (9:1, v/v) to afford target compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With carbon tetrabromide; triethylamine In acetonitrile at 20℃; for 6h; | General procedure for the synthesis of 2-aminothiazoles 3 General procedure: To a mixture of ketone (0.5 mmol), thiourea (0.5 mmol), and triethylamine (0.5 mmol) in acetonitrile (3 mL) was added carbon tetrabromide (0.5 mmol) in a round bottom flask at room temperature and the reaction mixture was stirred for 2-6 h. After completion of the reaction (monitored by TLC), water (5 mL) was added and the mixture was extracted with EtOAc (3*5 mL). The combined organic phase was dried over MgSO4, filtered, and evaporated under reduced pressure to give the crude product. The resulting product was purified by silica gel column chromatography using a gradient mixture of hexane/ethyl acetate as eluent to afford an analytically pure sample of 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With sodium carbonate; ammonium chloride In neat (no solvent) for 1h; Milling; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16% | Stage #1: (4-fluoro-phenyl)-thiourea; methyl iodide In methanol at 0 - 20℃; for 0.5h; Stage #2: 3-chloro-3-oxopropanoic acid methyl ester With 4-methyl-morpholine In dichloromethane at -5 - 20℃; Inert atmosphere; | 4 3-(4-fluorophenyl)-6-hydroxy-2-(methylthio)pyrimidin-4(3H)-one (N) 3-(4-fluorophenyl)-6-hydroxy-2-(methylthio)pyrimidin-4(3H)-one (N): To a suspension of l-(4-fluorophenyl)-2-thiourea (L) (2.30 g, 13.5 mmol, 1.0 eq.) in methanol (30 mL) at 0 °C was added iodomethane (1.01 mL, 16.2 mmol, 1.2 eq.). The mixture was stirred for 30 min at rt until a clear solution was obtained. Solvent was removed and the residue was dried in vacuo for 1 h. The residue was dissoved in DCM (50 mL), cooled to -5 °C and 4- methylmorpholine (2.97 mL, 27.0 mmol, 2.0 eq.) was added followed by the dropwise addition of methyl malonyl chloride (M) (2.17 mL, 20.2 mmol, 1.5 eq.). The resulting mixture was stirred at rt overnight under nitrogen. The mixture was cooled to -5 °C and additional amounts of 4- methylmorpholine (0.50 mL, 4.5 mmol, 0.33 eq.) and methyl malonyl chloride (0.50 mL, 4.7 mmol, 0.35 eq.) were added. The mixture was continued to stir at rt for 2 h and cooled to 10 °C. Water (25 mL) and DCM (25 mL) were added. The mixture was stirred for 30 min. The interfacial solid was filtered, washed with water and dried in a vacuum oven to provide 557 mg (16%) of the title compound as a white solid. 1H MR (400 MHz, DMSO-i) δ 11.95 (bs, 1H), 7.41-7.34 (m, 4H), 5.28 (s, 1H), 2.40 (s, 3H). ES-MS [M+l]+: 253.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46.98% | With triethylamine; In N,N-dimethyl-formamide; toluene; at 120.0℃; for 6.0h; | To the reactor was added 200 mg (1 mmol) of <strong>[87080-27-1]licorice chalcone A</strong> and 130.77 mg (1.3 mmol) 1- (4-fluorophenyl) thiourea,Add 50ml of toluene and 5mLDMF as the reaction solvent, add 0.5mL of triethylamine as a catalyst, heating sets heated to 120Lt; 0 & gt; C, followed by magnetic stirring for 6 hours. The residue was analyzed by thin layer chromatography. After completion of the reaction, the residue was concentrated under reduced pressure and subjected to column chromatography and dryingBrown powder (136.21 mg), total yield 46.98% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium acetate In ethanol at 78℃; for 2h; | 5.1 Synthesis of 2-(p-fluorophenyl)imino-1,3-thiazolidin-4-one In a clean 50 mL single-necked flask, 4.0 mmol of N-(4-fluorophenyl)thiourea was added, 15.0 mL95% ethanol, stirring by adding 5.20mmol of anhydrous sodium acetate, 5.3mmol of ethyl chloroacetate, gradually heated to 78 °C , reflux reaction 2.0hThe reaction mixture was cooled to room temperature to precipitate a white solid, evacuated,To give the product 2- (p-fluorophenyl) imino-1,3-thiazolidin-4-one (0.79 g), m.p. 230-232 °C, and the crude yield was 100.0%. | |
With sodium acetate In ethanol Reflux; | 3.2.2. General Procedure for Synthesis of 2-arylimino-1,3-thiazolidin-4-one derivatives (3) General procedure: A mixture of aryl thiourea (2) (0.04 mol) in 16.45 mL ethanol (95%) was refluxed with fused sodium acetate (0.052mol) and ethyl chloroacetate (5.65 mL) for about 4-5 h. The reaction mixture was then poured onto ice cold water and was kept overnight for complete precipitation. The precipitates obtained were filtered, dried and crystallized from ethanol(95%) [34, 35]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | Stage #1: (4-fluoro-phenyl)-thiourea; 3-(2-bromo-4,4-dimethyl-3-oxopentyl)-quinolin-2(1H)-one In ethanol for 2h; Reflux; Stage #2: With ammonium hydroxide In ethanol for 0.5h; Reflux; | 6 Preparation of 3-((4-tert-butyl-2-(4-fluorophenylamino)thiazol-5-yl)methyl)quinolin-2(1H)-one 10 mmol of 3-(2-bromo-4,4-dimethyl-3-oxopentyl)quinolin-2(1H)-one, 5 ml of absolute ethanol, dissolved after adding 10mmol 4-fluorophenyl thiourea, reflux 2.0h, aqueous ammonia was added dropwise pH = 8 ~ 9, then refluxed for 0.5h, remove part of the solvent, cooled, precipitated solid, filtered, washed with 95% ethanol and dried to give 3-((4-tert-butyl-2-(4-fluorophenylamino)thiazol-5-yl)methyl)quinolin-2(1H)-one, yield 45% |
45% | In ethanol for 4h; Reflux; | 4.1.3. General procedure for the synthesis of target compounds (A1-A28) General procedure: Compound 5 (1 mmol) was added into a refluxing solution of anappropriate aryl thiourea (1.2 mmol) in EtOH (15 mL) and refluxed for4 h. After completion of the reaction as indicated by TLC, the mixturewas cooled to room temperature. The reaction mixture made alkalinewith NH3 (aq) to pH = 8-9 and stirred for 30 min, then the reactionmixture was cooled and filtered to get the crude products. The crudeproducts were recrystallized from 95% alcohol to offer compounds A1-A28. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With hydrogenchloride In ethanol; water at 105℃; for 4h; | 39 Preparation 393- (4-Fluoro-phenyl) -2-thioxo-2,4 (1H, 3H) -pyrimidinedione-5-carboxylate: 2.54 g (15.0 mol) of 4-fluorophenylthiourea and 3.2 mL (13.8 mol)Of DEMM were successively added to a mixed solution of 3.2 mL of concentrated hydrochloric acid and 9.6 mL of ethanol,The reaction was refluxed at 105 ° C for 4 h.TLC trace detection to the end of the reaction.After cooling,The solid was collected and washed with ethanol.That is to get 4.12gWhite solid 3- (4-fluoro-phenyl) -2-thioxo-2,4 (1H, 3H) -pyrimidinedione-5-carboxylate (Compound 2,Corresponding to (d) in the reaction scheme), yield 94%. |
64% | With hydrogenchloride In ethanol; water for 6h; Reflux; | 4.1; 56.1 Step 1: Ethyl 3-(4-fluorophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5- carboxylate (56-1) : A mixture of diethyl 2-(ethoxymethylene)malonate (3.2 mL, 13.8 mmol), 1-(4- fluorophenyl)-thiourea (2.54 g, 15 mmol), and HCl (36% aq, 3.2 mL) in EtOH was refluxed for 6 h. The reaction was cooled to room temperature and filtered. The resulting solid was washed with EtOH and dried to give Compound 56-1 (2.6 g, 64% yield). MS for C13H11FN2O3S: m/z 295 (MH+) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | at 120℃; for 0.166667h; Microwave irradiation; | 3 Example 3 2-(4-fluorophenylimino)-7-ethoxy-4,5,6,7-tetrahydrobenzo[d]thiazole 2 mmol of 1-(4-fluorophenyl)thiourea and 2 mmol of 7-oxabicyclo[4.1.0]heptan-2-one were added to 10 mL of ethanol, and the reaction was carried out until the reaction was carried out under microwave at 120 ° C. After heating in a minute or oil bath to reflux for 12 hours, TLC followed the progress of the reaction. After the reaction was completed, the reaction mixture was concentrated, and the title compound was obtained as a white solid, with a microwave yield of 90% and an oil bath yield of 86%. . |
86% | Sealed tube; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tetra-N-butylammonium tribromide at 20℃; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With polymer supported zinc(II)-salen complex In ethanol; water 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. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | In ethanol at 80℃; | 1 Example 1. Preparation ofN-(4-bromophenyl)-4-phenylthiazol-2-amine (PA1, compound 1), N-(4-fluorophenyl)-4-phenylthiazol-2-amine (PA2, compound 2), N-(4- fluorophenyl)-4-(pyridin-3-yl)thiazol-2-amine (PA3, compound 3), and N-(4-bromophenyl)-4- (pyridin-3-yl)thiazol-2-amine (PA5, compound 4). Referring to Scheme 1, 2-bromo-l -phenyl ethan-1 -one (1.0 equivalent, 0.5 mmol) and l-(4- fluorophenyl)thiourea (1.0 equivalent, 0.5 mmol) were premixed in 2.5 mL of ethanol each in a separate vial. The mixture was pumped through a preheated glass microfluidic reactor (Syrris Asia Flow Chemistry Module) at a predetermined flow rate to have the desired residence time using Syrris Asia pump. The outcome was collected in a flask and concentrated under reduced pressure. The crude was dissolved in 10 mL ethyl acetate washed with 2 x 10 mL satd. NaHC03. The organic phase was combined, dried MgS04 and concentrated under reduced pressure. The crude obtained was purified using prepacked silica cartridge on Teledyne CombiFlash R 200. Elution with 10:90 hexane-ethyl acetate afforded PA2 in 97% yield. The product was obtained as a colorless powder 1H MR (CDCI3) δ 8.16 (s, 1H), 7.86 - 7.74 (m, 2H), 7.45 - 7.22 (m, 5H), 7.04 - 6.94 (m, 2H) and 6.78 (s, 1H); 13C NMR (101 MHz, CDC13) δ 165.99, 160.25, 157.84, 151.52, 136.71, 136.68, 134.60, 128.73, 128.07, 126.29, 121.10, 121.02, 116.28, 116.05 and 101.67. The same methodology was used to synthesize other three compounds PA1, PA3 and PA5. For PA1, The product was obtained as a colorless powder, Yield 98% (162 mg). 1H MR (CDC13) δ 8.35 (s, 1H), 7.87 - 7.78 (m, 2H), 7.42 - 7.29 (m, 5H), 7.23 - 7.16 (m, 2H) and 6.83 (s, 1H); 13C NMR (101 MHz, CDC13) δ 164.56, 151.46, 139.52, 134.46, 132.30, 128.79, 128.17, 126.32, 119.85, 115.19 and 102.15. For PA3, The product was obtained as a pale yellow powder, Yield 94% (128 mg). 1H NMR (C2D6SO) δ 10.36 (s, 1H), 9.14 (dd, 7= 2.3, 0.8 Hz, 1H), 8.51 (dd, 7= 4.8, 1.6 Hz, 1H), 8.25 (dt, 7= 8.0, 1.9 Hz, 1H), 7.81 - 7.69 (m, 2H), 7.52 (s, 1H), 7.55 - 7.41 (m, 1H) and 7.26 - 7.14 (m, 2H); 13C NMR (C2D6SO) 6 163.65, 158.09, 155.73, 148.42, 147.12, 146.96, 137.57, 137.54, 132.76, 130.07, 123.70, 118.51, 118.43, 115.64, 115.42 and 104.51. For PA5, The product was obtained as a yellowish powder, Yield 95% (158 mg). 1H NMR (C2D6SO) δ 10.49 (s, 1H), 9.14 (dd, 7= 2.3, 0.9 Hz, 1H), 8.52 (dd, 7= 4.8, 1.6 Hz, 1H), 8.26 (ddd, 7= 8.0, 2.3, 1.7 Hz, 1H), 7.76 - 7.68 (m, 2H) and 7.59 - 7.38 (m, 4H); 13C NMR (C2D6SO) δ 163.16, 148.47, 147.21, 146.98, 140.31, 132.80, 131.72, 130.00, 124.78, 123.71, 118.83, 112.45 and 105.03. |
82% | With triethylamine In ethanol Reflux; | 47.2 47.2 Preparation of 2-(4-fluorophenylimino)-4-phenylthiazole 25mL solane flask was added 1mmol N-(4-fluorophenyl) thiourea,1.05 mmol of alpha-bromoacetophenone, dissolved in 10 mL of ethanol and added with 1.5 mmol of triethylamine,Reflux reaction. After TLC tracking reaction, the temperature of the reaction solution was lowered to room temperature.The solvent was distilled off under reduced pressure, and the residue was subjected to column chromatography (eluent: petroleum ether-ethyl acetate) to obtain the target compound.White solid, yield 82%. |
at 80℃; Flow reactor; Green chemistry; |
In tetrahydrofuran at 20℃; for 0.5h; | ||
128 mg | In water at 20℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In tetrahydrofuran at 20℃; for 0.5h; | |
In tetrahydrofuran at 20℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With erythrosine B; oxygen In acetonitrile at 20℃; for 16h; Irradiation; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With iron(III) sulphate monohydrate; sodium acetate at 20℃; for 2h; | 2.2 General procedure for the preparationof arylcyanamide General procedure: To a stirred solution of DMSO (4-5 mL), respectiveisothiocyanate (2 mmol) was added slowly at roomtemperature and stirring further continued for 3 h atroom temperature. The progress of the reaction wasinvestigated by TLC (20% ethylacetate in hexane).After forming the respective substituted thiourea (asper TLC) Fe2(SO4)3.H2O (50 mol %, 417 mg) andNaOAc (2 mmol, 164 mg) were added to that solutionat room temperature, then the reaction mixture wasstirred for 2 h. During this time black color precipitate(FeS) was observed. And it was removed by centrifugation. The clear solution was concentrated byusing a rotary evaporator and the crude mixture waspurified by silica gel (60-120 mesh) column chromatographyusing Ethylacetate in Hexane as eluent toobtain a phenyl cyanamide as a white solid. |
204 mg | With cobalt(II) sulfate monohydrate; sodium acetate In N,N-dimethyl-formamide at 20℃; for 2h; | Synthesis of cyanamides 2a-h,l-n (General method). General procedure: Aryl/alkyl isothiocyanate 1a-h,l-n (2 mmol) was addedslowly to stirred DMF (4-5 ml), followed by addition ofaqueous NH3 (2 ml, 2 mmol) at room temperature. Thereaction mixture was stirred for 1 h at room temperature.Thiourea formation was monitored by TLC on silica gel.Then CoSO4·H2O (121 mg, 0.5 mmol, 25 mol %) wasadded slowly followed by addition of NaOAc (164 mg,2 mmol), and the reaction mixture was stirred for 2 h atroom temperature. During this time, black precipitate(CoS) appeared and was removed by centrifugation. Theclear solution was concentrated using rotary evaporator,and the crude mixture was purified by columnchromatography using 10% EtOAc in hexane as eluent toobtain a corresponding cyanamide as a target product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: (4-fluoro-phenyl)-thiourea With iron(III) sulphate monohydrate; triethylamine In dimethyl sulfoxide at 20℃; for 2h; Stage #2: With sodium azide In dimethyl sulfoxide at 20℃; for 3h; regioselective reaction; | Representative experimental procedure for the synthesis of phenylamino tetrazole General procedure: Substituted thiourea (2mmol, 304mg) was completely dissolved in the DMSO (3 mL) at room temperature. To this, Et3N (2mmol, 202mg) and catalyst were added slowly at room temperature. The resulting reaction mixture was stirred at room temperature for 2 h. After that, NaN3 (2mmol, 130mg) was added, and stirring was further continued for 3 h. The development of the reaction was examined by TLC (30% ethyl acetate in hexane). The black color solid, which was observed during the reaction, separated using the centrifugation process. The clear reaction mixture extracted with ethyl acetate (2×10 mL), and the organic layer was washed with brine (1×5mL) and water (2×5mL). Drying and evaporation of the solvent gave a residue that was purified by column chromatography using 30% ethyl acetate in hexane as eluent to obtain phenyl aminotetrazole as a solid. |
Multi-step reaction with 2 steps 1: cobalt(II) sulfate monohydrate; sodium acetate / N,N-dimethyl-formamide / 2 h / 20 °C 2: sodium azide / N,N-dimethyl-formamide / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol at 20℃; for 0.5h; | 2-Amino-5-bromothiazole derivatives synthesis General procedure: To a solution of the intermediate thioureas (1 eq., 0.1 M) in EtOH was added 2-bromoacetophenone (1.25 eq). The solution was stirred at room temperature until completion of the reaction followed by TLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol at 20℃; for 0.5h; | 2-Amino-5-bromothiazole derivatives synthesis General procedure: To a solution of the intermediate thioureas (1 eq., 0.1 M) in EtOH was added 2-bromoacetophenone (1.25 eq). The solution was stirred at room temperature until completion of the reaction followed by TLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol at 20℃; for 0.5h; | 2-Amino-5-bromothiazole derivatives synthesis General procedure: To a solution of the intermediate thioureas (1 eq., 0.1 M) in EtOH was added 2-bromoacetophenone (1.25 eq). The solution was stirred at room temperature until completion of the reaction followed by TLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol at 20℃; for 0.5h; | 2-Amino-5-bromothiazole derivatives synthesis General procedure: To a solution of the intermediate thioureas (1 eq., 0.1 M) in EtOH was added 2-bromoacetophenone (1.25 eq). The solution was stirred at room temperature until completion of the reaction followed by TLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol at 20℃; for 0.5h; | 2-Amino-5-bromothiazole derivatives synthesis General procedure: To a solution of the intermediate thioureas (1 eq., 0.1 M) in EtOH was added 2-bromoacetophenone (1.25 eq). The solution was stirred at room temperature until completion of the reaction followed by TLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 190℃; Microwave irradiation; | 3.1.2. General procedure for the synthesis of thiazole derivatives (3a-j) General procedure: Substituted thiourea (1 mmol) and 3-chloropentane-2,4-dione(1 mmol) were placed in an open vessel microwave (Discover CEM, 300W and temperature control set at 190 °C measured withan IR sensor) for 4-5 min. Reaction progress was checked by TLCusing hexane: ethyl acetate (7: 3) as mobile phase. After completionof the reaction, 10 mL of ethanol was added to the reaction mixtureand the resulting mixture was further added to ice cold water toform desired product (3a-j). The precipitates were filtered andpurified by recrystallization from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With potassium carbonate In neat (no solvent) at 50 - 60℃; Green chemistry; | Preparation of 4-(1-naphthyl)-2-amino/arylaminothiazoles (4) General Procedure General procedure: A mixture of 1-(-tosyloxy)acetonaphthone (2, 3.28g, 10 mmol) and thiourea/substituted thiourea (10 mmol) was ground in a pestle mortar in the presence of pinch of K2CO3 and heated at 50-60 oC. The resulting solid was filtered, washed with water (2-3 times) and recrystallized from ethanol to give pure 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With poly(ethylene) glycol-600 at 20℃; Green chemistry; | General procedure for the synthesis of 5 from 1, 2 via 3 General procedure: mixture of 1 (10 mmol), 2 (10 mmol) and PEG-600(30 mL) was stirred at RT for 4-5 h. Then, salicylaldehyde(10 mM) and l-proline (25 mol %) was added into the samereaction vessel and the reaction mixture was stirred at RTfor a period of 2-3 h. After completion of the reaction, asshown by TLC analysis, the mixture was poured into icecoldwater (60 mL). The separated solid was filtered, washedwith water (2 × 30 mL) and air-dried at RT. The crude productwas recrystallized from suitable solvent to obtain pure 5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | In ethanol at 80℃; for 2h; Sealed tube; | 4.6.1. Procedure 1: general procedure for the synthesis of aminothiazoles and thiazoles (1-18, 22-31, 32-34, 48-50, 52-53) General procedure: A solution of appropriate arylthiourea (1 eq.) or arylthioamide(1 eq.) and aryl-2-bromoethanone (1 eq.) in anhydrous ethanol washeated in a sealed tube at 80 C for 2 h. The progress of reactionwasmonitored by TLC. Ethanol was removed from the reaction mixtureand the resulted residue was washed with aq. NaHCO3. Theaqueous layer was extracted with CH2Cl2 (3 times) and the combinedorganic layer was dried over anhydrous Na2SO4. The filtratewas concentrated in vacuo and the crude product was purified onTeledyne Isco Combiflash Rf purification machine to afford correspondingthiazoles in moderate to good yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | In ethanol at 80℃; for 2h; Sealed tube; | 4.6.1. Procedure 1: general procedure for the synthesis of aminothiazoles and thiazoles (1-18, 22-31, 32-34, 48-50, 52-53) General procedure: A solution of appropriate arylthiourea (1 eq.) or arylthioamide(1 eq.) and aryl-2-bromoethanone (1 eq.) in anhydrous ethanol washeated in a sealed tube at 80 C for 2 h. The progress of reactionwasmonitored by TLC. Ethanol was removed from the reaction mixtureand the resulted residue was washed with aq. NaHCO3. Theaqueous layer was extracted with CH2Cl2 (3 times) and the combinedorganic layer was dried over anhydrous Na2SO4. The filtratewas concentrated in vacuo and the crude product was purified onTeledyne Isco Combiflash Rf purification machine to afford correspondingthiazoles in moderate to good yields. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: (4-fluoro-phenyl)-thiourea With iron(III) sulphate monohydrate; triethylamine In dimethyl sulfoxide at 20℃; for 2h; Stage #2: With ammonium hydroxide In dimethyl sulfoxide at 20℃; for 3h; regioselective reaction; | Representative experimental procedure for the synthesis of phenylguanidines General procedure: Et3N (2mmol, 202mg), catalyst (50mol %), and thiourea (2mmol) were stirred in DMSO at room temperature, and the reaction mixture was stirred for 2 h. After that, Aq NH3(2mL) was added, and further stirring was continued for 3 h. The progress of the reaction was monitored by TLC using 30% ethyl acetate in hexane as eluent. After completion of the reaction, the target reaction mixture was centrifuged for 10 min by using a centrifugation machine to separate the black color solid. The clear solution mixture extracted with ethyl acetate (2×10 mL), and the organic layer was washed with brine (1×5mL) and water (2×5mL). Drying and evaporation of the solvent gave a residue that was purified by column chromatography using 30% ethyl acetate in hexane as eluent to obtain phenyl aminoguanidine as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With sodium carbonate In ethanol at 25 - 30℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium carbonate In ethanol at 25 - 30℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With sodium carbonate In ethanol at 25 - 30℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sodium carbonate In ethanol at 25 - 30℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In ethanol for 4h; Reflux; | General method for the synthesis of aminothiazole target compounds (1-31). General procedure: A solution of2-bromo-1-(3-fluoro-4-(4-methyl-1H-imidazol-1-yl)phenyl)ethanone (I, 100 mg, 1 eq) andcorresponding thioureas (35-65,1 eq) was stirred in absolute ethanol (8 mL) heated to reflux for4 h. After completion of reaction as indicated in TLC, the reaction mixture was cooled to roomtemperature, and the solvent removed by rotavapor. The residue was finally purified by columnchromatography (DCM: methanol: 2.5: 97.5) to yield 1-31 as solids (60-97%). |
Tags: 459-05-2 synthesis path| 459-05-2 SDS| 459-05-2 COA| 459-05-2 purity| 459-05-2 application| 459-05-2 NMR| 459-05-2 COA| 459-05-2 structure
[ 404-52-4 ]
1,3-Bis(4-fluorophenyl)thiourea
Similarity: 0.97
[ 791594-33-7 ]
1-(3,5-Difluorophenyl)thiourea
Similarity: 0.94
[ 62644-14-8 ]
1-(3-Fluorophenyl)-3-methylthiourea
Similarity: 0.94
[ 404-52-4 ]
1,3-Bis(4-fluorophenyl)thiourea
Similarity: 0.97
[ 791594-33-7 ]
1-(3,5-Difluorophenyl)thiourea
Similarity: 0.94
[ 62644-14-8 ]
1-(3-Fluorophenyl)-3-methylthiourea
Similarity: 0.94
[ 404-52-4 ]
1,3-Bis(4-fluorophenyl)thiourea
Similarity: 0.97
[ 791594-33-7 ]
1-(3,5-Difluorophenyl)thiourea
Similarity: 0.94
[ 62644-14-8 ]
1-(3-Fluorophenyl)-3-methylthiourea
Similarity: 0.94
[ 404-52-4 ]
1,3-Bis(4-fluorophenyl)thiourea
Similarity: 0.97
[ 791594-33-7 ]
1-(3,5-Difluorophenyl)thiourea
Similarity: 0.94
[ 62644-14-8 ]
1-(3-Fluorophenyl)-3-methylthiourea
Similarity: 0.94
[ 404-52-4 ]
1,3-Bis(4-fluorophenyl)thiourea
Similarity: 0.97
[ 791594-33-7 ]
1-(3,5-Difluorophenyl)thiourea
Similarity: 0.94
[ 62644-14-8 ]
1-(3-Fluorophenyl)-3-methylthiourea
Similarity: 0.94
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 :