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CAS No. : | 1192-58-1 | MDL No. : | MFCD00003087 |
Formula : | C6H7NO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | OUKQTRFCDKSEPL-UHFFFAOYSA-N |
M.W : | 109.13 | Pubchem ID : | 14504 |
Synonyms : |
|
Num. heavy atoms : | 8 |
Num. arom. heavy atoms : | 5 |
Fraction Csp3 : | 0.17 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 31.08 |
TPSA : | 22.0 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) : | -6.64 cm/s |
Log Po/w (iLOGP) : | 1.29 |
Log Po/w (XLOGP3) : | 0.46 |
Log Po/w (WLOGP) : | 0.84 |
Log Po/w (MLOGP) : | -0.18 |
Log Po/w (SILICOS-IT) : | 0.95 |
Consensus Log Po/w : | 0.67 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.2 |
Solubility : | 6.84 mg/ml ; 0.0627 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.49 |
Solubility : | 35.3 mg/ml ; 0.323 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.05 |
Solubility : | 9.66 mg/ml ; 0.0885 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.0 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H227-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | To dimethylformamide (3.9 mL, 50.40 mmol) in a 3-necked round-bottom flask fitted with an internal temperature probe at 5 C was added phosphorous oxychloride (4.6 mL, 50.40 mmol) dropwise at a rate such that the internal temperature did not exceed 20 C. After completion of the addition, 20 mL anhydrous 1 ,2-dichloroethane was added and the reaction mixture stirred at room temperature until homogeneous. N-methylpyrrole (4.1 mL, 45.82 mmol) was added dropwise as a solution in 4 mL 1 ,2-dichloroethane at a rate such that the internal temperature did not exceed 35 C. After the addition was complete, the reaction mixture was heated to reflux for 15 minutes, then cooled to room temperature. An aqueous solution of potassium acetate (5.5 M, 46 mL) was added slowly and the mixture stirred vigorously at reflux for 5 minutes. After cooling to room temperature, organics were extracted with ether (3 chi 75 mL), washed with saturated sodium bicarbonate (3 x 75 mL), brine (75 mL), dried over magnesium sulfate, filtered and concentrated to give 4.75 g of brown liquid. The crude liquid was purified by distillation with a Kugelrohr apparatus to give 1 -methyl- lH-pyrrole-2-carbaldehyde (3.22 g, 64%) as a pale pink liquid. Used without further characterization. To a solution of 1 -methyl- lH-pyrrole-2-carbaldehyde (1.09 g, 10.0 mmol) in 60 mL chloroform at -20 C was added a single crystal of iodine. The mixture was stirred until homogeneous. Bromine (0.51 mL, 10.0 mmol) was added dropwise as a solution in 10 mL chloroform. The solution was stirred while warming from -20 to 0 C over 1.5 h. Chloroform was removed in vacuo and the residue added to 5% sodium bisulfite solution to quench excess bromine/iodine. Saturated sodium bicarbonate was added until the pH of the mixture reached 7. Organics were extracted with ether (3 chi 75 mL), dried over magnesium sulfate, filtered and concentrated to give crude 4-bromo-l -methyl- lH-pyrrole-2-carbaldehyde (1.80 g) as the major component of a mixture of starting aldehyde and dibromopyrrole. Used without further purification. l-Methyl-4-(3,3,3-trifluoropropyl)-lH-pyrrole-2-carbaldehyde (23 mg, ca. 13% over two steps) was synthesized as in Example 3.1 using 4-bromo-l -methyl- lH-pyrrole-2- carbaldehyde (crude mixture, ca. 92 mg, 0.49 mmol) in place of 5-bromo-2-formylfuran and potassium (3,3,3-trifluoro)propyl trifluoroborate (125 mg, 0.61 mmol) in place of hexylboronic acid. Used without further characterization. | |
With trichlorophosphate; at 0℃;Heating / reflux; | 1 -Methyl- 1 H-pyrrole-2-carboxaldehyde (19) was prepared according to standard method for Villsmeier reaction, using POCI3, DMF and 1-methylpyrrole. The product was obtained in pure form by repeated fractional distillation, and stored over Zn powder and KOH pellets. 1H-NMR (CDCl3) 69.50 (s, IH, CHO), 6.87-6.84 (2 x d, 2H, Py-CH), 6.16 (d, IH, J = 3.9 Hz, Py-CH), 3.90 (s, 3H, CH3). EI-HRMS: m/z calcd for C6H7NO 109.0528, found 109.0531 (100%), 81.0540 (40%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 73% 2: 8% | Stage #1: N-Methylpyrrole; Vilsmeier reagent at 0℃; for 1h; Reflux; Stage #2: With water; sodium carbonate at 0℃; | |
With sodium hydroxide 1) DMF, 20 deg C, 18 h; Yield given. Multistep reaction. Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; pyrophosphoryl chloride 1) 20 deg C, 18 h; Yield given. Multistep reaction. Yields of byproduct given; | ||
With sodium hydroxide; trichlorophosphate 1) 20 deg C, 18 h; Yield given. Multistep reaction. Yields of byproduct given; | ||
Stage #1: N-Methylpyrrole; N,N-dimethyl-formamide With trichlorophosphate In 1,1-dichloroethane for 1h; Reflux; Stage #2: With potassium hydroxide In 1,1-dichloroethane; water for 0.0166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | Potassium /c/7-butoxide (5.76 g, (0211) 51.31 mmol) was added to a stirring solution of triethyl phosphonacetate (8.73 ml, 43.98 mmol) in tetrahydrofuran (THF, 350.0 mL) and the mixture was stirred at 0 C for 30 min. A solution of A-methyl-2-pyrrolecarboxaldehyde 1 (4.00 g, 36.65 mmol) in THF (350.0 mL) was added to the resultant solution and the mixture was stirred at 22 C for 48 h. The mixture was quenched with saturated NH4Cl (aq) and extracted twice with ethyl acetate (EtOAc). The combined organic layer was dried over anhydrous MgS04 and the filtrate was condensed under reduced pressure, followed by silica-gel flash column chromatography to afford compound 2 (5.55 g, 30.97 mmol, 84%, Rs= 0.30 (EtO Ac/Hexane = 1 :4)) as a yellow oil. (0212) NMR (400 MHz, CDCb) d 7.59 (d, J= 15.9 Hz, 1H), 6.73 (br t, J= 2.1 Hz, 1H), 6.65 (dd, j= 3.9, 1.2 Hz, 1H), 6.17-6.12 (m, 2H), 4.23 (q, j= 7.2 Hz, 2H), 3.70 (s, 3H), 1.32 (t, J= 7.2 Hz, 3H). 13C NMR (100 MHz, CDCb) d 167.9, 132.3, 129.4, 127.0, 112.8, 112.0, 109.4, 60.2, 34.5, 14.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With bismuth (III) nitrate pentahydrate; In water; at 80℃; for 0.166667h;Microwave irradiation; Green chemistry; | General procedure: The substrate (o-phenylenediamine, 1.0 mmol), aldehyde(1.1 mmol) and bismuth nitrate pentahydrate (24 mg, 5 mol%) were mixed together with water (1mL) in a microwave vial fitted with a magnetic stir bar.The mixture was irradiated in an automated microwave(CEM Corporation, Discover model) and the progressof the reaction was monitored by TLC. After completionof the reaction (Table 4) ethyl acetate (10 mL) wasadded to the reaction mixture and the organic layer waswashed with saturated sodium bicarbonate solution,brine and water successively. It was dried over anhydroussodium sulfate and the solvent was removed underreduced pressure. The crude mass was purifiedthrough a small silica gel column using ethyl acetate/hexanes as eluent. |
71% | With sodium metabisulfite; In ethanol; water; for 4h; | General procedure: To a mixture of 2-pyridine aldehyde (5a, 107 mg, 1mmol) and 1,2-diaminobenzene (6a, 108 mg, 1 mmol) in ethanol (25 mL)was added an aqueous solution of sodium pyrosulfite (1.52g, 8 mmol, 5 mL) and refluxed for 4 to 6 h, until the TLC indicated that reaction was completed. The reaction mixture was concentrated under vacuum and the residue was dissolved in CHCl3 (2 x15 mL) and washed with water. The combined organic phases were dried over anhydrousNa2SO4, filtered and the solvent was removed under vacuumand purified by column chromatography (70% EtOAc-hexane) to afford compound 7a as a brown solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.7% | With acetic acid; In toluene; at 120℃; for 16h; | [1-METHYL-2-PYRROLECARBOXALDEHYDE] (500 mg, 4. [58] mmol) was dissolved in 10 mL of toluene followed by addition of [1-TRIPHENYLPHOSPHORANYLIDENE-2-PROPANONE] (1. [53] g, 4. [81MMOL)] and 10 drops of acetic acid. The reaction mixture was heated to [120 C] in a sealed tube for 16 h. The reaction mixture was cooled to room temperature and the solvent was evaporated. The residue was dissolved in EtOAc, and the organic phase was washed with saturated [NAHC03] solution and brine. The organic phase was dried over anhydrous [NA2S04,] filtered, and concentrated. The residue was purified by column chromatography on silica gel to yield 565 mg (82.7%) of the vinyl ketone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With N1,N4-bis(3-(triethoxysilyl)propyl) butane-1,4-diaminium dichloride immobilized on magnetic nano gamma-Fe2O3(at)SiO2; In water; at 80℃; for 0.116667h; | General procedure: In a 10-mL round-bottomed flask, a mixture of aldehyde (1.0 mmol), malononitrile (or ethyl cyanoacetate) (1.1 mmol), and gamma-Fe2O3(at)SiO2(at)[Bis-APTES]Cl2 NPs (5 mg) in water (3.0 mL) was stirred at 80 C for appropriate time. After reaction completion as monitored by TLC [n-hexane:EtOAc (7:3)], the precipitate was dissolved in ethanol or acetone (20 mL). Then, the nanocatalyst was removed using an external magnet. After that, the solvent was evaporated and the solid residue was washed with a few drops of cold ethanol and washed with water. The expected product was obtained in high yield purity without need for any extra purification steps. Physical and spectral data of newly synthesized compound 2-((1-Methyl-1H-pyrrol-2-yl)methylene)malononitrile Yellow crystals; m.p. 156- 158 C; IR (KBr, cm- 1): 3386, 3118, 3032, 2924, 2854, 2212, 1586, 1491, 1402, 1318, 1183, 1170, 752; 1H NMR (400 MHz, DMSO-d6) delta (ppm) = 3.80 (s, 3H), 6.46 (ddd, J1 = 4.4 Hz, J2 = 2.0 Hz, J3 = 0.4 Hz, 1H), 7.40 (dd, J1 = 4.4 Hz, J2 = 1.2 Hz, 1H), 7.51 (t, J = 1.2 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) delta (ppm) = 34.0, 67.7, 112.6, 115.2, 115.9, 119.0, 127.2, 134.3, 145. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With hydroxylamine hydrochloride; In 1-methyl-pyrrolidin-2-one; ice-water; | Step 1 Synthesis of 2-cyano-N-methylpyrrole (22-4) N-methyl-2-pyrrolcarboxaldehyde (5 g) and hydroxylamine hydrochloride (3.82 g) were mixed in 1-methyl-2-pyrrolidinone (50 ml) and the mixture was refluxed at 110 C. for 2 hours. After confiring the completion of the reaction, to the reaction mixture was slowly added an ice-water (200 ml) and the resulting mixure was extracted with ethyl acetate (150 ml*3), washed with brine, dried over sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure and the obtained residue was purified by column-chromatography (ethyl acetate/hexane={fraction (1/4)}) to yield the compound 22-4 (3.5 g, 72%). 1H NMR(300 MHz, CDCl3): delta 6.79(m, 2H), 6.16(m, 1H), 3.78(s, 3H) |
65.81% | (Step 1) (1053) To a solution of 1-methyl-1H-pyrrole-2-carbaldehyde (5.0 g, 45.82 mmol) in pyridine (34.5 mL) was added hydroxylamine hydrochloride (6.368 g, 91.63 mmol) at room temperature, and the mixture was stirred at 95C for 10 min. Then, acetic anhydride (27.5 mL) was added thereto, and the mixture was stirred at 95C for 2 hr. To the reaction mixture was added water, and the precipitate was collected by filtration. The obtained crude product was purified by silica gel column chromatography (solvent; 5% ethyl acetate/hexane) to give 1-methyl-1H-pyrrole-2-carbonitrile (3.2 g, 65.81%) as a colorless oil. 1H-NMR(400MHz,DMSO-d6):delta3.76(s,3H),6.14(dd,1H,J=2.84,3.56Hz),6.75-6.78(m,2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; water; | Preparation 5A To a suspension of 0.9 g. (1.02 mole) of lithium aluminum hydride in 50 ml. of THF at 0 C. under a nitrogen atmosphere was added a solution of 2.0 ml. (0.02 mole) of 1-methylpyrrol-2-carboxaldehyde. When the strongly exothermic reaction had subsided, the reaction mixture was cooled to 0 C. and quenched by the careful addition of 10 ml. of water. The reaction mixture was dried over magnesium sulfate, filtered and taken to dryness in vacuo to give 2.0 g. of 2-hydroxymethyl-1-methylpyrrole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With hydroxylamine hydrochloride; sodium acetate; In methanol; water;Reflux; | All of the oxime substrates used in this investigation were synthesized in quantitative yields by refluxing a mixture of 1 equiv of the corresponding ketones or aldehydes, 1.6 equiv of hydroxylamine hydrochloride, and 2.0 equiv of sodium acetate in aqueous methanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With nitric acid; In water; at -70 - -20℃; for 1h; | To 100 mL of 90% HNO3 cooled to -70 0C for 30 min, was added dropwise neat 1 -methylpyrrole-2- carboxaldehyde (25 g, 250 mmol). The temperature inside the reaction flask was carefully monitored and maintained between -50 and -30 0C during addition. After complete addition, the reaction mixture was allowed to warm up to -20 0C for 30 min, followed by pouring the materials onto ice. The precipitated product was collected by filtration and recrystallized from 1PrOH to afford 27 g of the title product (70% yield). 1H-NMR (CDCl3) 69.61 (s, IH, CHO), 7.70 (d, IH, J = 1.8 Hz, Py-CH), 7.41 (d, IH, J = 1.8 Hz, Py-CH), 4.01 (s, 3H, CH3). 13C-NMR (125 MHz, CDCl3) 6180.5 (+, C), 131.3 (+, C), 129.7 (-, CH), 126.5 (+, C), 117.8 (-, CH), 38.1 (-, CH3). EI-HRMS: m/z calcd for C6H6N2O3 154.0378, found 154.0380 (100%), 126.0377 (25%). |
49.6% | With sodium hydroxide; nitric acid; In ice-water; acetic acid; | Step 1 Synthesis of N-methyl-4-nitro-pyrrol-2-carboxaldehyde (22-1) N-methylpyrrol-2-carboxaldehyde (5 g) was dissolved in anhydrous acetic acid (50 ml), and to an ice-cold of the solution was slowly added dropwise nitric acid (1.84 ml) with stirring. The mixture was stirred at this temperature for I hour, and then at room temperature for 18 hours. After confiing the completion of the reaction, to the mixture was added an ice-water (200 ml), followed by slowly adding solid sodium hydroxide (20 g) thereto and stirring for 1 hour. The obtained mixture was extracted with ether (150 ml*3). The obtained organic layer was washed with aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure and purified by column-chromatography (ethyl acetatelhexane={fraction (1/4)}) to yield the compound 22-1 (3.5 g, 49.6%). 1H NMR(300 MHz, CDCl3): delta9.63(s, 1H), 7.68(s, 1H), 7.43(s, 1H), 4.03(s, 3H) |
22% | With nitric acid; acetic anhydride; In water; at -25 - 20℃; for 2.33333h; | (i) 1 -Methyl-4-nitro- lH-pyrrole-2-carbaldehgammade(See, for example, Suckling, C. J., Khalaf, A.I., Pitt A.R., Scobie, M.,Tetrahedron, 2000, 56, 5225.) HNO3 (70%) (1.6 mL) was added dropwise to acetic anhydride (8 mL) at -25C, and allowed to stir for a further 20 min. This solution was added dropwise to a solution of l-methylpyrrole-2-carboxaldehyde (Aldrich) (1.74 g, 15.96 mmol), in acetic anhydride (12 mL) at -250C and allowed to return to RT over 2 h. The solution was cooled to -4O0C, at which point a precipitate formed. The precipitate was collected and washed with hexane and then dried under reduced pressure to the sub-title compound (0.540 g, 22%). m.p. = 157-1590C, (Lit = 158-1600C). <n="57"/>1H NlVlR (CDCl3): 4.04 (3H, s, CH3), 7.43 (IH, d, Ar-H, J=1.6Hz), 7.68 (IH, d, Ar-H, J=I.6Hz).IR (KBr): 3139 upsilon(N-Me), 3125 upsilon(Ar-H), 2958 upsilon(C-H(COH)), 1671 upsilon(C=O), 1504, 131I u(N=O) Cm"1. Anal. Calcd. For C6H6O3N2 C, 46.76; H, 3.92; N, 18.18; O, 31.14, Found: C, 46.29; H, 3.68; N, 17.47. |
19% | With nitric acid; acetic anhydride; | (1) 1-methyl-4-nitro-pyrrole-2-aldehyde (22) Acetic anhydride (25 ml) solution of fuming nitric acid (1.5 ml, 37.5 mmol) was cooled at -30 C. Acetic anhydride (10 ml) solution of 1-methylpyrrole-2-carboxyaldehyde (21) (3.27 g, 30.0 mmol) was dropwisely added under the same temperature, and the mixture was stirred at the same temperature for 5 hours. The precipitated solid was filtered to obtain nitro compound (22) (860 mg, 19%). |
16% | With nitric acid; In ethanol; water; acetic anhydride; | 1-Methyl-4-nitropyrrol-2-carboxyaldehyde A solution of 25 g (0.23 mol) of 1-methylpyrrole-2-carboxyaldehyde in 200 ml of acetic anhydride was cooled to -40 C. Fuming nitric acid (17.6 g) was added dropwise to the solution over 30 minutes, followed by stirring at -40 C. for 1 hour and at -10 C. for additional 2 hours. The reaction mixture was added with ice and allowed to stand over night. The reaction mixture was extracted with ethyl acetate and then neutralized with sodium hydrogencarbonate. The solvent was then distilled out under reduced pressure. The residue was purified by chromatography on a silica gel column (ethyl acetate/n-hexane =1/2) and then crystallized from a 5:1 mixture of ethanol and water, whereby 5.67 g of the title compound were obtained as brown crystals (yield: 16%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sodium ethanolate In tetrahydrofuran at 20℃; for 16h; | |
86% | With potassium hydroxide In ethanol at 20℃; for 0.133333h; Sonication; Green chemistry; | Ultrasound method General procedure: A mixture of 2,3-dihydro-1H-inden-1-one (1, 10 mmol), and hetero-aromatic/aromatic aldehyde (2, 10 mmol), 5 cm3 ethanol were taken in a 25 cm3Pyrex flask. To this reaction mixture, equimolar amount of KOH was added. The colour of the solution turned into dark yellow/brown after addition of KOH. The alkaline mixture was exposed to ultrasound irradiation at room temperature until the formation of products (checked by TLC). The reaction mass was allowed to cool at room temperature, then added into beaker containing ice-cold water, acidified, filtered, dried and recrystallized using ethanol solvent. (Note: In all three methods, the reaction mixture was not acidified when one of the reactant was either 2-pyridinecarboxaldehyde or 4-pyridinecarboxaldehyde.) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | With N-Bromosuccinimide; In tetrahydrofuran; at 0℃; for 4h; | Into a 100-mL 3-necked round-bottom flask was placed 1 -methyl-1H-pyrrole- 2-carbaldehyde (1 g, 9.16 mmol, 1.00 equiv) in tetrahydrofuran (10 mL). This was followed by the addition of NBS (1.64 g, 9.21 mmol, 1.10 equiv) in several batches with stirring at 0oC. The resulting solution was stirred for 4 h at 0oC. The mixture was washed with 1x100 mL of water. The solution was extracted with 2x80 mL of ethyl acetate and the organic layers were combined. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 0.3 g (17%) of 5-bromo-1-methyl-1H-pyrrole-2-carbaldehyde as a white solid. Chemical Formula: C6H6BrNO ; LCMS: 188. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; mesitylenesulfonylhydroxylamine; | EXAMPLE 73 7-Bromo-2-(1-methyl-1H-pyrrol-2-yl)-[1,2,4]triazolo[1,5-a]pyridin-5-ylamine The title compound, MS m/e (%): 294 (M++2, 100), was prepared in accordance with the general method of example 63 from <strong>[329974-09-6]4-bromo-pyridine-2,6-diamine</strong>, O-mesitylene-sulfonylhydroxylamine, and 1-methylpyrrole-2-carboxaldehyde. The purification was performed with reversed phase HPLC eluting with an acetonitrile/water gradient. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With Aliquat 336; sodium hydroxide; at 20 - 110℃; for 4h; | Example 3 BSc4327: 4,6-Bis((E)-2-(1-methyl-1H-pyrrol-2-yl)vinyl)pyrimidine Synthesis: <strong>[1558-17-4]<strong>[1558-17-4]4,6-Dimethylpyrimidin</strong>e</strong> (150 mg, 1.38 mmol), 1-Methyl-1H-pyrrole-2-carbaldehyde (302.3 mg, 2.77 mmol) and aliquat 336 (55 mg, 0.13 mmol) are dissolved in 5M NaOH-solution (15 ml). The solution is heated to boiling point for 1 h at 110 C., subsequently stirred for 3 h at room temperature. The solution is filtered and purified by column chromatography (Axel Semrau FlashMaster Cy/EE gradient). Obtained are 162 mg BSc4327 (40%) as yellow solid.1H-NMR (CDCL3, 300 MHz): delta=8.98 (s, 1H), 7.86 (d, J=15.5 Hz, 2H), 7.00 (s, 1H), 6.73 (q, m, 6H), 6.21 (m, 2H), 3.77 (s, 6H) ppm.13C-NMR (CDCl3, 125 MHz): delta=162.7, 158.5, 130.8, 125.9, 124.4, 121.4, 116.1, 110.0, 109.1, 108.3, 34.3 ppmMS (ESI) m/z=289.2 (M+(-1)), 275.2, |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With potassium acetate; In N,N-dimethyl acetamide; at 150℃; for 17h;Inert atmosphere; Schlenk technique; | General procedure: In a typical procedure, the aryl bromide (1 mmol), pyrrole (2mmol), and KOAc (2 mmol) were introduced in a Schlenk tube,equipped with a magnetic stirring bar. The catalyst [eitherPdPPy,5 or Pd(OAc)2 at 0.02-2.0 mol%] and DMAc (2.5 ml)were added, and the Schlenk tube was purged several timesusing vacuum/argon flow. The Schlenk tube was placed in a preheatedoil bath at 150 C, and reactants were allowed to stir for17 h. The reaction mixture was analyzed by GC and NMR todetermine the conversion of aryl bromide. The solvent was thenremoved by heating the reaction vessel under vacuum, and theresidue formed was charged directly onto a silica gel column.The products were eluted, using an appropriate ratio of EtOAcand heptane. Recycling procedure were based on simplePdPPy powder paper filtration, rinsing with a small portion oforganic solvent, and drying under vacuum at 60 C for 4 h. Subsequentcatalytic tests were conducted using DMAc at 150 C inthe presence of KOAc and sufficient PdPPy collected fromseveral experiments |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With tetrabromo[1,1'-butylene-3,3'-bis(N-2-(diisopropylaminoethyl)benzimidazol-2-ylidene)]dipyridinedipalladium(II); potassium acetate; In N,N-dimethyl acetamide; at 120℃; for 2h;Inert atmosphere; Schlenk technique; | General procedure: Heteroarene derivarive (2.0 mmol), aryl bromide (1.0 mmol),KOAc (2.0 mmol), and DMA (2 mL) were added to an oven driedSchlenk tube under argon atmosphere. Subsequently, the bimetallicpalladium-NHC catalyst (2a-2c) (0.005 mmol, 0.5 mol%) was addedto stirred solution in a Schlenk tube, and the closed Schlenk tubewas stirred at 120 C for 2 h. End of the reaction, the solution was cooled to room temperature and dichloromethane (2 mL) was thenadded to the crude mixture. This solution was used for GC analysis and yields (%) were calculated according to aryl bromide. |
88%Chromat. | With dibromo-[1,3-bis(3,5-di-tert-butylbenzyl)benzimidazole-2-ylidene](pyridine)palladium(II); potassium acetate; In N,N-dimethyl acetamide; at 120℃; for 1h;Inert atmosphere; Schlenk technique; | General procedure: An oven dried Schlenk flask was charged with aryl halide(1.0 mmol), 1-methylpyrrole-2-carboxaldehyde (2.0 mmol), KOAc(1.5 mmol), palladium-NHC-PEPPSI complex (0.01 mmol) andDMAc (2 mL). The Schlenk tube was purged several times withargon and it was placed in a preheated oil bath at 120 C, and thereaction mixture was stirred for different durations given in thespecific tables. At the end of the reaction, the solvent was removedunder vacuum, and the residue was charged directly onto a silicagel column. The products were eluted by using n-hexane/diethylether mixture (5:1, v/v). The yields were established by GC and GCMSbased on aryl halides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With tetrabromo[1,1'-butylene-3,3'-bis(N-2-(diisopropylaminoethyl)benzimidazol-2-ylidene)]dipyridinedipalladium(II); potassium acetate; In N,N-dimethyl acetamide; at 120℃; for 2h;Inert atmosphere; Schlenk technique; | General procedure: Heteroarene derivarive (2.0 mmol), aryl bromide (1.0 mmol),KOAc (2.0 mmol), and DMA (2 mL) were added to an oven driedSchlenk tube under argon atmosphere. Subsequently, the bimetallicpalladium-NHC catalyst (2a-2c) (0.005 mmol, 0.5 mol%) was addedto stirred solution in a Schlenk tube, and the closed Schlenk tubewas stirred at 120 C for 2 h. End of the reaction, the solution was cooled to room temperature and dichloromethane (2 mL) was thenadded to the crude mixture. This solution was used for GC analysis and yields (%) were calculated according to aryl bromide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With tetrabromo[1,1'-butylene-3,3'-bis(N-2-(diisopropylaminoethyl)benzimidazol-2-ylidene)]dipyridinedipalladium(II); potassium acetate; In N,N-dimethyl acetamide; at 120℃; for 2h;Inert atmosphere; Schlenk technique; | General procedure: Heteroarene derivarive (2.0 mmol), aryl bromide (1.0 mmol),KOAc (2.0 mmol), and DMA (2 mL) were added to an oven driedSchlenk tube under argon atmosphere. Subsequently, the bimetallicpalladium-NHC catalyst (2a-2c) (0.005 mmol, 0.5 mol%) was addedto stirred solution in a Schlenk tube, and the closed Schlenk tubewas stirred at 120 C for 2 h. End of the reaction, the solution was cooled to room temperature and dichloromethane (2 mL) was thenadded to the crude mixture. This solution was used for GC analysis and yields (%) were calculated according to aryl bromide. |
60% | With potassium carbonate;palladium diacetate; In ISOPROPYLAMIDE; at 21℃;Reflux; Inert atmosphere; | l-Methyl-5-aryl-lH-pyrrole-2-carboxaldehydes were generally prepared accordingly:[0205] To a mixture of l-methyl-2-pyrrole-carboxaldehyde 40 (0.408 mL. 4.0 mmol), substituted arylbromide (2.0 mmol), palladium diacetate (2.25 mg, 0.01 mmol) and 2CO3 (552 mg, 4.0 mmol) was added DMAc (6 mL) at 21 C under an argon atmosphere. The reaction mixture was refluxed for overnight. The mixture was then cooled and diluted with ethyl acetate (100 mL). The organic layer was washed with water (2 X 20 mL), then dried with brine and MgSC>4 and concentrated in vacuo. Flash column chromatography on silica gel (n-hexanes : ethyl acetate = 20: 1) of the residue afforded l-methyl-5-aryl-lH-pyrrole-2- carboxaldehyde. |
35% | With potassium acetate; In N,N-dimethyl acetamide; at 150℃; for 17h;Inert atmosphere; Schlenk technique; | General procedure: In a typical procedure, the aryl bromide (1 mmol), pyrrole (2mmol), and KOAc (2 mmol) were introduced in a Schlenk tube,equipped with a magnetic stirring bar. The catalyst [eitherPdPPy,5 or Pd(OAc)2 at 0.02-2.0 mol%] and DMAc (2.5 ml)were added, and the Schlenk tube was purged several timesusing vacuum/argon flow. The Schlenk tube was placed in a preheatedoil bath at 150 C, and reactants were allowed to stir for17 h. The reaction mixture was analyzed by GC and NMR todetermine the conversion of aryl bromide. The solvent was thenremoved by heating the reaction vessel under vacuum, and theresidue formed was charged directly onto a silica gel column.The products were eluted, using an appropriate ratio of EtOAcand heptane. Recycling procedure were based on simplePdPPy powder paper filtration, rinsing with a small portion oforganic solvent, and drying under vacuum at 60 C for 4 h. Subsequentcatalytic tests were conducted using DMAc at 150 C inthe presence of KOAc and sufficient PdPPy collected fromseveral experiments |
68%Chromat. | With dibromo-[1,3-bis(3,5-di-tert-butylbenzyl)benzimidazole-2-ylidene](pyridine)palladium(II); potassium acetate; In N,N-dimethyl acetamide; at 120℃; for 1h;Inert atmosphere; Schlenk technique; | General procedure: An oven dried Schlenk flask was charged with aryl halide(1.0 mmol), 1-methylpyrrole-2-carboxaldehyde (2.0 mmol), KOAc(1.5 mmol), palladium-NHC-PEPPSI complex (0.01 mmol) andDMAc (2 mL). The Schlenk tube was purged several times withargon and it was placed in a preheated oil bath at 120 C, and thereaction mixture was stirred for different durations given in thespecific tables. At the end of the reaction, the solvent was removedunder vacuum, and the residue was charged directly onto a silicagel column. The products were eluted by using n-hexane/diethylether mixture (5:1, v/v). The yields were established by GC and GCMSbased on aryl halides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With tetrabromo[1,1'-butylene-3,3'-bis(N-2-(diisopropylaminoethyl)benzimidazol-2-ylidene)]dipyridinedipalladium(II); potassium acetate; In N,N-dimethyl acetamide; at 120℃; for 2h;Inert atmosphere; Schlenk technique; | General procedure: Heteroarene derivarive (2.0 mmol), aryl bromide (1.0 mmol),KOAc (2.0 mmol), and DMA (2 mL) were added to an oven driedSchlenk tube under argon atmosphere. Subsequently, the bimetallicpalladium-NHC catalyst (2a-2c) (0.005 mmol, 0.5 mol%) was addedto stirred solution in a Schlenk tube, and the closed Schlenk tubewas stirred at 120 C for 2 h. End of the reaction, the solution was cooled to room temperature and dichloromethane (2 mL) was thenadded to the crude mixture. This solution was used for GC analysis and yields (%) were calculated according to aryl bromide. |
68% | With potassium acetate; In N,N-dimethyl acetamide; at 150℃; for 17h;Inert atmosphere; Schlenk technique; | General procedure: In a typical procedure, the aryl bromide (1 mmol), pyrrole (2mmol), and KOAc (2 mmol) were introduced in a Schlenk tube,equipped with a magnetic stirring bar. The catalyst [eitherPdPPy,5 or Pd(OAc)2 at 0.02-2.0 mol%] and DMAc (2.5 ml)were added, and the Schlenk tube was purged several timesusing vacuum/argon flow. The Schlenk tube was placed in a preheatedoil bath at 150 C, and reactants were allowed to stir for17 h. The reaction mixture was analyzed by GC and NMR todetermine the conversion of aryl bromide. The solvent was thenremoved by heating the reaction vessel under vacuum, and theresidue formed was charged directly onto a silica gel column.The products were eluted, using an appropriate ratio of EtOAcand heptane. Recycling procedure were based on simplePdPPy powder paper filtration, rinsing with a small portion oforganic solvent, and drying under vacuum at 60 C for 4 h. Subsequentcatalytic tests were conducted using DMAc at 150 C inthe presence of KOAc and sufficient PdPPy collected fromseveral experiments |
69%Chromat. | With dibromo-[1,3-bis(3,5-di-tert-butylbenzyl)benzimidazole-2-ylidene](pyridine)palladium(II); potassium acetate; In N,N-dimethyl acetamide; at 120℃; for 1h;Inert atmosphere; Schlenk technique; | General procedure: An oven dried Schlenk flask was charged with aryl halide(1.0 mmol), 1-methylpyrrole-2-carboxaldehyde (2.0 mmol), KOAc(1.5 mmol), palladium-NHC-PEPPSI complex (0.01 mmol) andDMAc (2 mL). The Schlenk tube was purged several times withargon and it was placed in a preheated oil bath at 120 C, and thereaction mixture was stirred for different durations given in thespecific tables. At the end of the reaction, the solvent was removedunder vacuum, and the residue was charged directly onto a silicagel column. The products were eluted by using n-hexane/diethylether mixture (5:1, v/v). The yields were established by GC and GCMSbased on aryl halides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With tetrabromo[1,1'-butylene-3,3'-bis(N-2-(diisopropylaminoethyl)benzimidazol-2-ylidene)]dipyridinedipalladium(II); potassium acetate; In N,N-dimethyl acetamide; at 120℃; for 2h;Inert atmosphere; Schlenk technique; | General procedure: Heteroarene derivarive (2.0 mmol), aryl bromide (1.0 mmol),KOAc (2.0 mmol), and DMA (2 mL) were added to an oven driedSchlenk tube under argon atmosphere. Subsequently, the bimetallicpalladium-NHC catalyst (2a-2c) (0.005 mmol, 0.5 mol%) was addedto stirred solution in a Schlenk tube, and the closed Schlenk tubewas stirred at 120 C for 2 h. End of the reaction, the solution was cooled to room temperature and dichloromethane (2 mL) was thenadded to the crude mixture. This solution was used for GC analysis and yields (%) were calculated according to aryl bromide. |
42% | With potassium acetate; In N,N-dimethyl acetamide; at 150℃; for 17h;Inert atmosphere; Schlenk technique; | General procedure: In a typical procedure, the aryl bromide (1 mmol), pyrrole (2mmol), and KOAc (2 mmol) were introduced in a Schlenk tube,equipped with a magnetic stirring bar. The catalyst [eitherPdPPy,5 or Pd(OAc)2 at 0.02-2.0 mol%] and DMAc (2.5 ml)were added, and the Schlenk tube was purged several timesusing vacuum/argon flow. The Schlenk tube was placed in a preheatedoil bath at 150 C, and reactants were allowed to stir for17 h. The reaction mixture was analyzed by GC and NMR todetermine the conversion of aryl bromide. The solvent was thenremoved by heating the reaction vessel under vacuum, and theresidue formed was charged directly onto a silica gel column.The products were eluted, using an appropriate ratio of EtOAcand heptane. Recycling procedure were based on simplePdPPy powder paper filtration, rinsing with a small portion oforganic solvent, and drying under vacuum at 60 C for 4 h. Subsequentcatalytic tests were conducted using DMAc at 150 C inthe presence of KOAc and sufficient PdPPy collected fromseveral experiments |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With potassium hydroxide; In methanol; at 0 - 20℃; for 24.5h; | General procedure: The general synthetic strategy employed to prepare the bichalcones through the piperazine Mannich base linkage analogs were based on the Claisen-Schmidt condensation. As shown in Scheme 2, a series of 23 bichalcones were prepared by base-catalyzed condensation of substituted Mannich bases of acetophenones with appropriate aldehydes in MeOH. To a stirred reaction mixture at 0 C was added a 30% solution of KOH (40 mL) dropwise over 30 min. The reaction mixture was kept at rt for 24 h, then diluted with water and extracted with EtOAc. Pure target compounds were obtained by silica gel column chromatography (cc) of the residue eluting with various solvent mixtures as indicated below. The structures of all the 23 bichalcones through the piperazine Mannich base linkage analogs were established on the basis of IR, 1H, 13C NMR, FABMS and HRFABMS. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With hydrogenchloride; In ethanol; water; at 80℃; for 18h; | General procedure: Into a round-bottom flask, equipped with a condenser and containing a suspension of 6 (2.0 mmol, 1 equiv) in ethanol (15 mL), was introduced the aldehyde (2.2 mmol, 1.1 equiv) and two drops of concentrated HCl. The reaction mixture was stirred and heated at 80 C for approximately 18 h. While cooling down the crude mixture in an ice bath, a precipitate was formed which was subsequently filtered off and washed with both water (2 × 10 mL) and cold ethanol (3 × 15 mL). The solid residue was then dried in vacuum at 60 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With hydrogenchloride; In ethanol; water; at 80℃; for 18h; | General procedure: Into a round-bottom flask, equipped with a condenser and containing a suspension of 6 (2.0 mmol, 1 equiv) in ethanol (15 mL), was introduced the aldehyde (2.2 mmol, 1.1 equiv) and two drops of concentrated HCl. The reaction mixture was stirred and heated at 80 C for approximately 18 h. While cooling down the crude mixture in an ice bath, a precipitate was formed which was subsequently filtered off and washed with both water (2 × 10 mL) and cold ethanol (3 × 15 mL). The solid residue was then dried in vacuum at 60 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With hydrogenchloride; In ethanol; water; at 80℃; for 18h; | General procedure: Into a round-bottom flask, equipped with a condenser and containing a suspension of 6 (2.0 mmol, 1 equiv) in ethanol (15 mL), was introduced the aldehyde (2.2 mmol, 1.1 equiv) and two drops of concentrated HCl. The reaction mixture was stirred and heated at 80 C for approximately 18 h. While cooling down the crude mixture in an ice bath, a precipitate was formed which was subsequently filtered off and washed with both water (2 × 10 mL) and cold ethanol (3 × 15 mL). The solid residue was then dried in vacuum at 60 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With piperidine In ethanol Inert atmosphere; Reflux; | 4.3. General procedure for the synthesis of compounds 1-5 General procedure: Compounds 1-5, all iodide salts, were obtained by refluxing in ethanol stoichiometric amounts (see Scheme 2) of 1,2-dimethylquinolinium iodide, 1,2,6-trimethylpyridinium iodide, 1,2-dimethyl-picolinium iodide, 1,4-dimethyl-picolinium iodide or 1,2,3-trimethylimidazolium iodide and the appropriate aldehyde in the presence of catalytic amount of piperidine. The resulting precipitates were recrystallized from ethanol. Details on the synthetic conditions and products characterization are reported below. |
63% | With piperidine In methanol for 2h; Reflux; | General procedure for the synthesis of mono-styryl dyes by Knoevenagel condensation General procedure: A mixture of the heterocyclic salt I17-I18 (1 mmol), aldehyde (1.5 mmol), and piperidine (0.10 mL, 1 mmol) in MeOH (5 mL) was heated under reflux for 2 h. After cooling toroom temperature, the precipitated solid was collected by filtration, washed with MeOH (2 × 5mL), Et2O (2 × 5 mL), dried and recrystallized from a suitable solvent (as indicated below), togive the analytically pure dye as an iodide salt. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With piperidine In ethanol Inert atmosphere; Reflux; | 4.3. General procedure for the synthesis of compounds 1-5 General procedure: Compounds 1-5, all iodide salts, were obtained by refluxing in ethanol stoichiometric amounts (see Scheme 2) of 1,2-dimethylquinolinium iodide, 1,2,6-trimethylpyridinium iodide, 1,2-dimethyl-picolinium iodide, 1,4-dimethyl-picolinium iodide or 1,2,3-trimethylimidazolium iodide and the appropriate aldehyde in the presence of catalytic amount of piperidine. The resulting precipitates were recrystallized from ethanol. Details on the synthetic conditions and products characterization are reported below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.19% | With sodium hydroxide; In ethanol; at 20℃; for 3.5h; | Half of mixture of 4-bromoacetophenone (1.5 g, 0.0079 mol) and1-methyl-1H-pyrrole-3-carbaldehyde (0.822 g, 0.0079 mol) inethanol was charged to 50% ethanolic solution (20 ml) of sodiumhydroxide (0.5 g, 0.0119 mol). The mixture was allowed to stir atroom temperature for 30 min followed by addition of remaininghalf portion. Stirring was continued for another 3 h. The precipitateproduced was filtered and washed with chloroform.Color: yellow, Mas: 290.155 g/mole. Yield: 88.19%, m.p. 144 C,1H-NMR (CDCl3) dppm: 7.87 (dd, 2H, Ar-H), 7.81 (d, 1H, Ar-H), 7.62(dd, 2H, Ar-H), 7.23 (dd, 1H, Ar-H), 6.85 (dd, 2H, Ar-H), 6.23 (q, 1H,Ar-H) 1.59 (s, 3H, CH3). 13C-NMR (CDCl3) dppm: 188.65, 137.51,132.71, 131.79, 130.17, 129.76, 128.19, 127.35, 115.87, 112.77, 109.95,34.41. UV(nm): lmax 314, Concentration 1.27 105 mol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With ammonium acetate In neat (no solvent) at 100℃; for 0.166667h; Microwave irradiation; Sealed tube; | 4.1.1.2. Microwave irradiation General procedure: A thoroughly mixed solvent-free mixture of the aldehyde 1 (0.55 g, 5 mmol), the appropriate ketone(5 mmol), ethyl cyanoacetate (0.57 g, 5 mmol) and ammonium acetate (3.1 g, 40 mmol), was subjected to microwave irradiation at 100 °C for 15 min. After being cooled to room temperature, the residue was treated with water, filtered, dried and recrystallized from ethanol. |
With ammonium acetate In ethanol Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: N-Methylpyrrole; 2,2,4-trimethyl-3,4-dihydroquinoline-1(2H)-carbaldehyde With trichlorophosphate In 1,1-dichloroethane for 1h; Reflux; Stage #2: With potassium hydroxide In 1,1-dichloroethane; water for 0.0166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: N-Methylpyrrole; N-isopropyl-N-phenylformamide With trichlorophosphate In 1,1-dichloroethane for 1h; Reflux; Stage #2: With potassium hydroxide In 1,1-dichloroethane; water for 0.0166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: N-Methylpyrrole; 2,2,6,6-tetramethylpiperidine-1-carboxaldehyde With trichlorophosphate In 1,1-dichloroethane for 1h; Reflux; Stage #2: With potassium hydroxide In 1,1-dichloroethane; water for 0.0166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With potassium tert-butylate; In dichloromethane; tert-butyl alcohol; at 20℃; for 3h;Inert atmosphere; | General procedure: 1,4-Diacetyl-piperazine-2,5-dione 2 (11.7 g, 50 mmol) was dissolved in dry CH2Cl2 (50 mL) under N2 atmosphere. Benzaldehyde (5 mL, 50 mmol) and potassium tert-butoxide (5.61 g, 50 mmol), dissolved in a minimum amount of tert-butanol (?25 mL), were added to this solution. The reaction mixture was stirred for 3 h, then a saturated aqueous solution of NH4Cl (100 mL) was added to quench the reaction and the mixture was extracted with ethyl acetate (100 mL). The organic phase was dried over anhydrous sodium sulfate, and concentrated in vacuo. The product 3a (11.2 g, 92%) was obtained as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With potassium tert-butylate; In N,N-dimethyl-formamide; at 80℃; for 4h; | Example 6 BSc4353: 2,5-Bis((E)-2-(1-methyl-1H-pyrrol-2-yl)vinyl)pyrazine Synthesis: <strong>[123-32-0]2,5-Dimethylpyrazine</strong> (0.125 g, 1.16 mmol) is dissolved in 10 ml dimethylformamide, followed by addition of 1-methyl-1H-pyrrol-2-carbaldehyde (0.252 g, 2.32 mmol) and potassium-t-butoxide (0.26 g, 2.32 mmol), and heated for 4 h to 80 C. and allowed to cool to room temperature. In this process, a solid crystallizes out. The solution containing the crystallized solid is filtered and washed with ethyl acetate. After drying under high-vacuum, 0.215 g (yield: 64%) of the product BSc4353 is obtained as orange-red solid.1H-NMR (CDCl3, 500 MHz): delta=8.40 (s, 2H), 7.62 (d, J=15.6 Hz, 2H), 6.88 (d, J=15.6 Hz, 2H), 6.70 (m, 2H), 6.65 (m, 2H), 6.19 (m, 2H), 3.76 (s, 6H) ppm.13C-NMR (CDCl3, 125 MHz): delta=147.8, 142.1, 130.5, 124.1, 120.6, 119.3, 107.9, 107.8, 33.3 ppm |
42% | With potassium tert-butylate; In N,N-dimethyl-formamide; at 0 - 20℃; | 2,5-dimethylpyrazine (0.5 g, 0.00462 mol) and 1-methylpyr-role-2-carboxaldehyde (1.513 g, 0.0138 mol) were dissolved in DMFand the mixture was cooled to 0 C (Scheme 1). To this mixture,potassium-tert-butanolate (1.55 g, 0.013 mol) were added in smallportions and the mixture was brought to ambient temperature andstirring was continued until all starting material had beenconsumed (TLC). After the completion of the reaction, waterwas added, and the product was isolated by extraction withchloroform. The organic layer was concentrated in vacuum and thesolid material obtained was recrystallized to give the product(1.2 g, 42%) as an orange solid. The structure of the compound wasconfirmed by IR and 1H and 13C NMR techniques.1H NMR (CDCl3, 500 MHz): delta = 3.7 (s, 6H), 6.16 (m, 2H), 6.64 (m,2H), 6.72 (m, 2H), 6.86 (d, 2H, J = 15.4 Hz), 7.60 (d, 2H, J = 15.4 Hz),8.42 (s,2H). 13C NMR (CDCl3, 150 MHz): delta = 34.2, 107.9, 108.2, 119.3,120.6, 122.1, 128.5, 140.1, 147.8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With acetic acid In methanol Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium sulfate In methanol at 50℃; for 48h; Inert atmosphere; | Ugi Products 5a-d; General Procedure General procedure: To a solution of pyrrole-2-carbaldehyde 1a,b (2 mmol) in MeOH (3 mL) were added successively Na2SO4 (0.3 g), the appropriate amine 2a-d (1.2 equiv), acid 3a (1.2 equiv), and isonitrile 4a,b (1.2 equiv) in a screw capped vial equipped with a magnetic stir bar. The reaction mixture was stirred at 50 °C for 24-48 h in a closed vial. After completion of the reaction (as indicated on TLC), the mixture was diluted with EtOAc (100 mL) and extracted with H2O (50 mL). The organic layer was washed with brine (50 mL), dried (MgSO4) and evaporated under reduced pressure to obtain a residue, which was subjected to silica gel column chromatography (50% EtOAc in heptane) to afford the desired products 5a-d (Table 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium sulfate In methanol at 50℃; for 48h; Inert atmosphere; | Ugi Products 5ad; General Procedure General procedure: To a solution of pyrrole-2-carbaldehyde 1a,b (2 mmol) in MeOH (3 mL) were added successively Na2SO4 (0.3 g), the appropriate amine 2ad (1.2 equiv), acid 3a (1.2 equiv), and isonitrile 4a,b (1.2 equiv) in a screw capped vial equipped with a magnetic stir bar. The reaction mixture was stirred at 50 °C for 2448 h in a closed vial. After completion of the reaction (as indicated on TLC), the mixture was diluted with EtOAc (100 mL) and extracted with H2O (50 mL). The organic layer was washed with brine (50 mL), dried (MgSO4) and evaporated under reduced pressure to obtain a residue, which was subjected to silica gel column chromatography (50% EtOAc in heptane) to afford the desired products 5ad (Table 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With piperidine; In ethanol; at 30℃; for 0.166667h;Microwave irradiation; | General procedure: Quinoline heterocycles were prepared according to the literature procedure [34]. Quaternary salts A were synthesized when a mixture of 0.016mmol quinoline heterocycles and 0.023mmol methyl iodide in ethanol was refluxed for 15h. After cooling, the product was filtered off and purified by recrystallization from EtOH. The dyes 1-13 were synthesized according to the literature [28,29]. The synthesis of dyes 14-20 followed the procedure [29] with slight modification. Various quaternary salts A (1mmol), aromatic aldehydes B (1mmol), 15mL anhydrous ethanol and a few drops of piperidine were mixed thoroughly together at ambient temperature in a dried round-bottom flask (50mL) equipped with a reflux condenser capped with an anhydrous CaCl2 drying tube. The mixture was subjected to microwave irradiation at appropriate time, power and temperature. After cooling, the crude products was filtered off and purified by two different methods depending on the dyes' solubility. For dyes 14-16, the crude products was recrystallized from EtOH-H2O to afford pure dyes. For dyes 17-20, having very poor solubility, the crude products was washed with diethyl ether and extracted with EtOH by Soxhlet extraction in 15h. The reaction details and yields of dyes 14-20 were listed in Table1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With piperidine; In ethanol; at 40℃; for 0.166667h;Microwave irradiation; | General procedure: Quinoline heterocycles were prepared according to the literature procedure [34]. Quaternary salts A were synthesized when a mixture of 0.016mmol quinoline heterocycles and 0.023mmol methyl iodide in ethanol was refluxed for 15h. After cooling, the product was filtered off and purified by recrystallization from EtOH. The dyes 1-13 were synthesized according to the literature [28,29]. The synthesis of dyes 14-20 followed the procedure [29] with slight modification. Various quaternary salts A (1mmol), aromatic aldehydes B (1mmol), 15mL anhydrous ethanol and a few drops of piperidine were mixed thoroughly together at ambient temperature in a dried round-bottom flask (50mL) equipped with a reflux condenser capped with an anhydrous CaCl2 drying tube. The mixture was subjected to microwave irradiation at appropriate time, power and temperature. After cooling, the crude products was filtered off and purified by two different methods depending on the dyes' solubility. For dyes 14-16, the crude products was recrystallized from EtOH-H2O to afford pure dyes. For dyes 17-20, having very poor solubility, the crude products was washed with diethyl ether and extracted with EtOH by Soxhlet extraction in 15h. The reaction details and yields of dyes 14-20 were listed in Table1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With acetic acid;Reflux; | General procedure: A solution of 1 (0.93 g, 5 mmol) and the appropriate aldehyde (5 mmol) in gl. acetic acid (15 mL) was refluxed for 6-8 h. The solid product separated upon cooling was filtered, washed with cold ethanol, dried and recrystallized. Physicochemical and analytical data are recorded in Table 3. IR (cm-1): 1690 - 1675 (C=O), 1640 - 1630 (C=N). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With ammonium acetate In neat (no solvent) at 100℃; for 0.25h; Microwave irradiation; Sealed tube; | 4.1.2.2. Microwave irradiation General procedure: A thoroughly mixed solvent-free mixture of the aldehyde 1 (0.55 g, 5 mmol), the appropriate ketone(5 mmol), malononitrile (0.33 g, 5 mmol) and ammonium acetate (3.1 g, 40 mmol), was subjected to microwave irradiation at 100 °C for 10 min. After being cooled to room temperature, the residue was treated with water, filtered, dried and recrystallized from ethanol. IR (cm-1): 3390-3240 (NH), 2225-2210 (CN). Yields and melting points are recorded in Table 1. |
50% | With ammonium acetate In ethanol Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | General procedure: 4.2.7. (4R)-4-Methyl-4-[(E)-2-phenylethenyl]-1,3-oxazolidin-2-one(9a) and (4S)-4-(diphenylphosphorylmethyl)-4-methyl-oxazolidin-2-one (13eo). Typical procedure of a Wittig reaction: To a suspensionof the phosphonium salt (13) (500 mg, 1.0 mmol, 2.0 equiv) in THF(5 mL) was added n-butyllithium (1.9 M in hexane, 1.0 mL,1.95 mmol, 3.9 equiv) at 78 C and then the solution was stirredfor 30 min at the same temperature. After the addition of benzaldehyde(54 mg, 0.5 mmol,1.0 equiv) at 78 C, the reaction mixturewas gradually warmed to ambient temperature and stirred for 2 h.After quenching with saturated aq NH4Cl (10 mL), the resultingbiphasic mixture was extracted with AcOEt (10 mL2). The combinedorganic layer was washed with water (10 mL) and brine(10 mL), dried over Na2SO4, filtered, and evaporated. Purification bysilica gel column chromatography (hexane:AcOEt3:1 to 1:1)provided 9a (101 mg, 99% yield, 98.6% ee) as a white solid, and 13-o(156 mg, 99% yield) as a white solid. The enantiomeric excess of 9awas determined by HPLC analysis by using the following condition.DAICEL CHIRALCEL IA column (4.6f150 mm), hexane:EtOH95:5(0 min)d50:50 (8.0 min), flow rate: 2.0 ml/min, temperature:25.0 C. The retention times of (S)-9a and (R)-9a were 4.6 min and5.3 min, respectively. (Compound 9a) mp: 155.6 C; [a]D20 61.0 (c0.27, CH3OH); 1H NMR (500 MHz, CDCl3) d ppm: 1.53 (s, 3H), 4.17 (d,1H, J8.3 Hz), 4.23 (d, 1H, J8.3 Hz), 5.09 (s, 1H), 6.21 (d, 1H,J16.1 Hz), 6.59 (d, 1H, J16.1 Hz), 7.26e7.36 (m, 5H); 13C NMR(126 MHz, CDCl3) d ppm; 25.6, 58.5, 76.5, 126.7, 128.3, 128.7, 130.1,131.2, 135.7, 159.0; IR (KBr) cm1: 3293, 1756, 1710, 1393, 1288, 1171,1042, 967, 751, 659; MS (ESI) m/z: 203 (M); Anal. Calcd forC12H13NO2: C, 70.92; H, 6.45; N, 6.89. Found: C, 70.80; H, 6.49; N,6.83. (Compound 13-o) mp: 181.4 C; [a]D20 9.1 (c 0.41, CH3OH); 1HNMR (500 MHz, CDCl3) d ppm: 1.34 (s, 3H), 4.09 (d, 1H, J8.8 Hz), 2.60e2.78 (m, 2H), 4.21 (d, 1H, J8.8 Hz), 6.44 (br s, 1H), 7.46e7.57(m, 5H), 7.67e7.71 (m, 2H), 7.78e7.82 (m, 2H); 13C NMR (126 MHz,CDCl3) d ppm; 26.7, 39.9 (d, J69.1 Hz), 57.3 (d, J4.8 Hz), 77.4 (d,J12.5 Hz), 128.9 (d, J3.6 Hz), 129.0 (d, J3.6 Hz), 130.3 (d,J9.5 Hz), 130.6 (d, J9.5 Hz), 132.2, 132.3, 132.8 (d, J90.6 Hz),133.6 (d, J93.0 Hz), 157.7; IR (KBr) cm1: 3308, 1758, 1439, 1255,1175, 1034, 930, 752, 699; HRMS (ESI): calcd for C17H19NO3P[MH] 316.1103; found 316.1105 | |
83% | General procedure: Typical procedure of a Wittig reaction: To a suspension of the phosphonium salt (13) (500 mg, 1.0 mmol, 2.0 equiv) in THF(5 mL) was added n-butyllithium (1.9 M in hexane, 1.0 mL,1.95 mmol, 3.9 equiv) at 78 C and then the solution was stirred for 30 min at the same temperature. After the addition of benzaldehyde(54 mg, 0.5 mmol,1.0 equiv) at 78 C, the reaction mixture was gradually warmed to ambient temperature and stirred for 2 h. After quenching with saturated aq NH4Cl (10 mL), the resulting biphasic mixture was extracted with AcOEt (10 mL2). The combined organic layer was washed with water (10 mL) and brine(10 mL), dried over Na2SO4, filtered, and evaporated. Purification bysilica gel column chromatography (hexane:AcOEt3:1 to 1:1)provided 9a (101 mg, 99% yield, 98.6% ee) as a white solid, and 13-o(156 mg, 99% yield) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With ammonium acetate In neat (no solvent) at 100℃; for 0.166667h; Microwave irradiation; Sealed tube; | 4.1.1.2. Microwave irradiation General procedure: A thoroughly mixed solvent-free mixture of the aldehyde 1 (0.55 g, 5 mmol), the appropriate ketone(5 mmol), ethyl cyanoacetate (0.57 g, 5 mmol) and ammonium acetate (3.1 g, 40 mmol), was subjected to microwave irradiation at 100 °C for 15 min. After being cooled to room temperature, the residue was treated with water, filtered, dried and recrystallized from ethanol. IR (cm-1): 3380-3220 (NH), 2220-2210 (CN), 1685-1675 (C=O). Yields and melting points are recorded inTable 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73.8% | With potassium tert-butylate; In neat (no solvent); at 20℃; for 2h;Milling; Green chemistry; | General procedure: In a grinding jar, 4-(diphenylamino)benzaldehyde (0.015 mol, 4.10 g) were combined with [(4-ethenylphenyl)methyl] phosphonic acid diethyl ester (0.01 mol, 2.53 g), t-BuOK (0.02 mol, 2.76 g) and the 7 mm stainless steel balls. The grinding jar was placed in a planetary ball-mill and stirred at 550 runs per minute during 2 h at room temperature. Then 60 mL DCM was added in the jar and the mixture was washed twice with 200 mL water. The organic layer was dried over MgSO4, concentrated under vacuum. The residue was isolated by column chromatography on silica gel using petroleum ether/ethyl acetate (10:1) to afford 3.06 g of the titled compound as a light yellow needle crystal. Yield 80.2%. |
73.8% | With potassium tert-butylate; In neat (no solvent); at 20℃; for 2h;Milling; | General procedure: 4-(Diphenylamino)benzaldehyde (15 mmol, 4.10 g), LSZ (10 mmol, 2.54 g), tBuOK (20 mmol, 2.24 g) and 7-mm stainless steel balls were placed in a grinding jar. The grinding jar was placed in a planetary ball-mill and stirred at 550 rotations perminute for 2 h at room temperature. The mixture became sticky and 60 mL CH2Cl2 was added to the jar, then the reaction mixture was washed twice with 200 mL water. The resulting organic layer was dried over MgSO4 and concentrated under vacuum. The residue was isolated by silica-gel column chromatography (light petroleum/ethyl acetate 10 : 1 v/v) to afford light-yellow needle crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With acetic acid; In ethanol; dimethyl sulfoxide;Reflux; | General procedure: A solution of 1.0 mmol of N-heterocyclic aldehyde in 10 mL of ethanol was added to a hot solution of 1.0 mmol of 5- or 6-aminouracil in 10 mL of DMSO. A few drops of glacial acetic acid were then added, and the mixture was refluxed for 6-8 h. The solution was cooled to room temperature, filtered, and evaporated to dryness using a rotary evaporator. The resulting solid was washed with cold ethanol followed by anhydrous diethyl ether. (E)-5-[(1-Methyl-1H-pyrrol-2-yl)methylidene]amino}pyrimidine-2,4(1H,3H)-dione (1). Yield 78%, light yellow powder, mp > 300C (decomp). 1H NMR spectrum, delta, ppm: 11.25 s and 10.96 s (1H each, NH), 9.08 s (1H, CH=N); 7.40 m, 6.99 m, 6.59 m, and 6.11 m (4H, 3?-H, 4?-H, 5?-H, 6-H); 3.88 s (3H, CH3). Found, %: C 55.57; H 4.55; N 25.74. C10H10N4O2. Calculated, %: C 55.04; H 4.62; N 25.68. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With potassium acetate; palladium diacetate; In N,N-dimethyl acetamide; at 150℃; for 16h;Inert atmosphere; | General procedure: The reaction of the triazole-substituted aryl bromide (1 mmol),heteroarene (1.5 mmol) and KOAc (0.196 g, 2 mmol) at 150 C during16 h in DMA (4 mL) in the presence of Pd(OAc)2 (2.24 mg,0.01 mmol) or PdCl(C3H5)(dppb) (6.1 mg, 0.01 mmol) (see Table orSchemes) under argon affords the coupling product after evaporationof the solvent and purification on silica gel. For procedures and NMRdata, see Electronic supplementary information. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With d(4)-methanol; 4-(diphenylphosphino)-1,3-bis(2,6-diisopropylphenyl)-1H-1,2,3-triazoliumhexafluorophosphate; potassium tert-butylate; at 90℃; for 12h;Glovebox; Inert atmosphere; | General procedure: In a glovebox, a reaction tube was charged with 1,2,3-triazolium salt A6H (7.2 mg, 0.01mmol), t-BuOK (6.7 mg, 0.06 mmol) and aldehyde or imine (0.2 mmol). The tube was sealedunder a N2 atmosphere, and anhydrous CD3OD (1 mL) was added. The solution was stirred at90 oC for 12h. The reaction mixture was concentrated in vacuo. When necessary, furtherpurification was performed by silica gel column chromatography: PE/AcOEt ?30/1 to 200/1,unless otherwise stated. |
65% | With (carbonyl)chloro(hydrido)tris(triphenylphosphine)ruthenium(II); water-d2; In toluene; at 100℃; for 0.5h;Inert atmosphere; Sealed tube; | General procedure: Aldehyde (0.3 mmol) and RuHCl(CO)(PPh3)3 (14.3 mg, 0.015 mmol, 5 mol%) were dissolved in PhMe(1.5 mL, 0.2 M) in an oven-dried screw-cap vial. D2O (27 muL, 1.5 mmol) was then added. The vial wassparged with argon and capped. The resulting solution was heated to 100 C and stirred for 30 minutes. Atthe end of the reaction, the solvent was removed in vacuo and crude material was purified by columnchromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With 1,10-Phenanthroline; copper(I) bromide dimethylsulfide complex; di-tert-butyl peroxide In 1,2-dichloro-ethane; <i>tert</i>-butyl alcohol at 120℃; for 16h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tetrabromo[1,1'-butylene-3,3'-bis(N-2-(diisopropylaminoethyl)benzimidazol-2-ylidene)]dipyridinedipalladium(II); potassium acetate; In N,N-dimethyl acetamide; at 120℃; for 2h;Inert atmosphere; Schlenk technique; | General procedure: Heteroarene derivarive (2.0 mmol), aryl bromide (1.0 mmol),KOAc (2.0 mmol), and DMA (2 mL) were added to an oven driedSchlenk tube under argon atmosphere. Subsequently, the bimetallicpalladium-NHC catalyst (2a-2c) (0.005 mmol, 0.5 mol%) was addedto stirred solution in a Schlenk tube, and the closed Schlenk tubewas stirred at 120 C for 2 h. End of the reaction, the solution was cooled to room temperature and dichloromethane (2 mL) was thenadded to the crude mixture. This solution was used for GC analysis and yields (%) were calculated according to aryl bromide. |
77%Chromat. | With dibromo-[1,3-bis(3,5-di-tert-butylbenzyl)benzimidazole-2-ylidene](pyridine)palladium(II); potassium acetate; In N,N-dimethyl acetamide; at 120℃; for 1h;Inert atmosphere; Schlenk technique; | General procedure: An oven dried Schlenk flask was charged with aryl halide(1.0 mmol), 1-methylpyrrole-2-carboxaldehyde (2.0 mmol), KOAc(1.5 mmol), palladium-NHC-PEPPSI complex (0.01 mmol) andDMAc (2 mL). The Schlenk tube was purged several times withargon and it was placed in a preheated oil bath at 120 C, and thereaction mixture was stirred for different durations given in thespecific tables. At the end of the reaction, the solvent was removedunder vacuum, and the residue was charged directly onto a silicagel column. The products were eluted by using n-hexane/diethylether mixture (5:1, v/v). The yields were established by GC and GCMSbased on aryl halides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23% | A 100mL round-bottomed flask was charged with <strong>[6882-68-4]sophoridine</strong> (1.24g, 5mmol), NaH (2.4g, 100mmol) and 50mL anhydrous tetrahydrofuran. The solution was stirred at room temperature for 1h and then N-substituted pyrrole-2-carboxyaldehyde 2 (2a-2u) (5mmol) was added followed by reflux for 48h. Reaction mixture was cooled and poured into water slowly (100mL). Reaction mixture was then extracted with dichloromethane (3×40mL). The organic phase was dried with anhydrous Na2SO4 and concentrated to give crude product. The residue was purified by silica gel flash column chromatography (methanol/dichloromethane, 1%) to afford 3a-3u in 23%-54% yields. | |
23% | With sodium hydride; In tetrahydrofuran; at 85℃; for 36h; | 2.4 g (100 mmol) of sodium hydride and 50 mL of anhydrous tetrahydrofuran were added to a 100 mL round bottom flask.Stir well, add 1.24 g (5 mmol) of <strong>[6882-68-4]sophoridine</strong>, slowly warm to 85 C, add 0.654 g (6 mmol) of N-methyl-2-pyrrolidine, and react for 36 h to the end point (TLC detection).After cooling to room temperature, excess sodium hydride was neutralized by dropwise addition of 3N hydrochloric acid.Dichloromethane extraction (40 mL×3), the organic phase was combined, dried over anhydrous Na2SO4.(V dichloromethane: V methanol = 50:1) was purified to give 0.389 g of light brown solid powder LYL-01: 14-(N-methyl-2-pyrrol-2-ylmethylene)<strong>[6882-68-4]sophoridine</strong>: yield 23%; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sodium hydrogencarbonate In N,N-dimethyl-formamide at 20 - 80℃; for 9h; Molecular sieve; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With piperidine; In ethanol; for 7h;Reflux; | General procedure: To a solution of 2-acetylnaphtho[2,3-b]furan-4,9-dione (1) (0.42mmol) in EtOH (5mL), piperidine (1.25mmol) and aromatic aldehydes (0.62mmol) were added. The reaction mixture was heated to reflux and stirred for 7h, then cooled to room temperature. The mixture was filtered and the filter cake was washed with 10mL of EtOH for three times, and dried under vacuum to give compounds 2a-d. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With potassium hydroxide In ethanol at 0 - 20℃; for 73h; Inert atmosphere; | General Procedure C: Synthesis of Chalcones (GP-C) General procedure: To a stirred solution of KOH (12.0 equiv) in absolute EtOH (100 mL) cooled to 0 °C in anice-bath was added dropwise a solution of the corresponding acetophenone (1.0 equiv) and aldehyde (1.0 equiv) in EtOH (20 mL). The reaction mixture was stirred at 0 °C for 1 h and then at room temperature for 72 h under a nitrogen atmosphere or until TLC analysis indicated complete consumption of starting material. The resulting mixture was then poured into ice-water (100 mL) and acidified to pH 3-4 with 3 M HCl. The aqueous solution was extracted with CHCl3 (3 × 100 mL) and the combined organic layer was washed with satd NaHCO3 (2 × 100 mL), brine (2 × 100 mL), dried over anhydrous MgSO4, filtered and the solvent removed under reduced pressure. The crude residue was purified by flash column chromatography over silica and/or recrystallized from MeOH or absolute EtOH to afford the corresponding chalcones. (E)-1-(4-Hydroxy-3-methoxyphenyl)-3-(1-methyl-1H-pyrrol-2-yl)prop-2-en-1-one (55). A mixture of pyrrole aldehyde 46 (3.30 mL, 30.7 mmol), acetophenone 37 (5.02 g, 30.2 mmol) and KOH (10.2 g, 182 mmol) in absolute EtOH (100 mL) was reacted according to GP-C. The crude residue was purified by flash column chromatography (SiO2, PE/EtOAc;5:1) and recrystallized from absolute EtOH to afford chalcone 55 (4.28 g, 55%) as a dark redbrownpowdery solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium cyanoborohydride; acetic acid; In methanol; at 20 - 50℃;pH 6-7; | General procedure: To a stirring solution of 8 (0.3 mmol) in MeOH (5 mL) was added the corresponding aldehyde (0.4 mmol) and NaCNBH3 (0.5 mmol)at room temperature. The mixture was adjusted to pH 6-7 by acetic acid, stirred overnight at room temperature, and quenched by 1M NaOH solution (5 mL). The mixture was diluted by H2O (15 mL), and extracted by DCM (10mL x 3). The combined organic layer waswashed by brine, dried over anhydrous MgSO4, filtered, and concentrated. The residue was purified over silica gel column(DCM: MeOH = 20 : 1) to yield oils 9b-s (70-93%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With 3,3'-(butane-1,4-diyl)bis(1-methyl-1H-imidazol-3-ium) hydrogen sulfate; In water; at 70℃; for 0.416667h;Green chemistry; | General procedure: A mixture of aromatic aldehyde 1 (1 mmol), (thio)barbituric acid 2 (1 mmol), and [C4 (MIm)2]·2Cl (0.025 g, 0.08 mmol) or [C4(MIm)2]·2HSO4 (0.010 g, 0.03 mmol) in water (4 mL) was stirred at 70 C. The progress of the reaction was monitored with TLC (ethyl acetate/n-hexane 4:1). After completion of the reaction, the crude product was filtered off and washed several times with water. After drying, the pure product was obtained, while there was no need to further purification process (5a-j). The spectral data of the new compound is as follow: 5-((1-methyl-1H-pyrrol-2-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (5j) Orange powder; m.p. 278-280 C (Dec.); FT-IR (KBr) 3115, 3060, 2906, 1695, 1640, 1385 cm-1; 1H NMR (400 MHz, DMSO-d6, 25 C, TMS) delta: 3.95 (s, 3H), 6.54 (dd, J1 = 4.4 Hz, J2 = 2.0 Hz, 1H), 8.79 (s, 1H), 8.26 (s, 1H), 8.56 (dd, J1 = 4.6 Hz, J2 = 1.6 Hz, 1H), 12.18 (s, 1H), 12.29 (s, 1H); 13C NMR (100 MHz, DMSO-d6, 25 C, TMS) delta: 34.4, 106.6, 112.5, 128.2, 129.6, 138.2, 149.7, 160.1, 162.8, 177.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39%; 39% | With formaldehyd; water; sodium hydroxide; at 120℃; for 0.5h;Microwave irradiation; | NaOH (0.50 g, 12.5 mmol), formaldehyde 1k (0.12 g, 4 mmol), aldehyde 1h (2 mmol) and water (400 muL) were placed in a glass 10 mL pressure vials and mixed. Reaction was carried out in microwave conditions: standard mode, 120 C, 30 min. After that reaction mixture was diluted by water (15 mL) and extracted with DCM (2 × 25 mL). Organic layer was dried under anhydrous MgSO4 and evaporated under reduce pressure. Alcohol 2h was obtained after purified by flash chromatography on silica gel in hexane : EtOAc 5 : 1. Water layer was diluted and acidify by 1N HCl (30 mL), and extracted by DCM (2 × 50 mL). Organic layer was dried under anhydrous MgSO4 and evaporated under reduce pressure to give pure acid 3h. (1-methyl-1H-pyrrole-2-yl)-methanol (2h). Yellow oil. Yield 39% (0.086 g) after flash chromatography hexane : EtOAc 5 : 1. 1H NMR (CDCl3, 700 MHz): delta 6.64 (dd, 1 H, JHH= 2.5 Hz, JHH= 1.8 Hz, CHAr), 6.11 (dd, 1 H, JHH= 3.5 Hz, JHH= 1.8 Hz, CHAr), 6.06 (dd, 1 H, JHH= 3.5 Hz, JHH= 2.7 Hz, CHAr), 4.57 (s, 2 H, CH2), 3.68 (s, 3 H, CH3). 13C NMR (CDCl3, 176 MHz): delta 131.9 (s, 1 C, CAr), 123.6 (s, 1 C, CArH), 108.9 (s, 1 C, CArH), 106.8 (s, 1 C, CArH), 56.7 (s, 1 C, CH2), 33.8 (s, 1 C, CH3). The analytical data are in agreement with those reported previously in the literature.[13] 1-Methyl-2-pyrrolecarboxylic acid (3h). Brown solid, mp 138-139 C (lit. 136-138 C). Yield 39% (0.098 g). 1H NMR (CDCl3, 700 MHz): delta 7.10 (dd, 1 H, JHH= 4.0 Hz, JHH= 1.8 Hz, CHAr), 6.84 (t, 1 H, JHH= 2.0 Hz, CHAr), 6.15 (dd, JHH= 4.0 Hz, JHH= 2.5 Hz, CHAr), 3.94 (s, 3 H, CH3). 13C NMR (CDCl3, 176 MHz): delta 166.3 (s, 1 C, CO), 130.8 (s, 1 C, CArH), 121.8 (s, 1 C, CAr), 120.1 (s, 1 C, CArH), 108.5 (s, 1 C, CArH), 37.1 (s, 1 C, CH3). The analytical data are in agreement with those reported previously in the literature.[14] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68.3% | General procedure: To a stirred solution of aromatic aldehyde (1.0 equiv, 2.4mmol) in DMSO (2mL), 1mL saturate sodium hydroxide solution was added and stirred for 30min. Then 2 (1.0 equiv, 2.4mmol) was added. Then stirred for another 6-8hat room temperature. Reaction was monitored by TLC. After completion, the reaction mixture was quenched with 5% aq. HCl and extracted with DCM, washed with water, dried over anhyd. Na2SO4 and concentrated under reduced pressure. The obtained crude product was purified by column chromatography. |
Tags: 1192-58-1 synthesis path| 1192-58-1 SDS| 1192-58-1 COA| 1192-58-1 purity| 1192-58-1 application| 1192-58-1 NMR| 1192-58-1 COA| 1192-58-1 structure
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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.
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