All Blogs | Help | Support | About
x This LabTrove instance has just been upgraded to 2.3, to see what new check out the documentation, http://www.labtrove.org/documentation/
14th November 2013 @ 18:11

reaction scheme

1-(4-methylphenyl)-2,5-dimethylpyrrole: p-Toluidine (0.562 g, 5.245 mmol) was combined with 2,5-hexanedione (0.530 mL, 4.518 mmol) and heated to 130º C overnight. The solution was allowed to cool and was then dissolved in ether (20 mL). Citric acid (20 mL, 10%) was added to the reaction. The bottom layer was extracted with ether (20 mL) and organic layers were combined. Organic layer was washed with H2O (15 mL) and the bottom aqueous layer was removed. Saturated NaCl (15 mL) was added to the solution and the bottom aqueous layer was separated. The organic layer was dried (MgSO4) and filtered. Filtered product was concentrated under reduced pressure. A stream of air was applied to the product, and the product was scraped until a solid formed. Recrystallization (ethanol) and vacuum filtration afforded a light brown solid (0.3243 g, 39%): Melting point 44.5º C - 45.5º C; FTIR 3033.95, 2987.29, 2919.29, 1913.44, 1625.31, 1582.40; 1H NMR (400 MHz, CDCl3) δ 7.247 (d, J= 8 Hz, 2H), 7.086 (d, J= 8 Hz, 2H), 5,884 (s, 2H), 2.415 (s, 3H), 2.019 (s, 6H).

 

1-(4-methylphenyl)-2,5-dimethylpyrrole-3-carboxaldehyde: Dimethylformamide (1 mL, 12.97 mmol) was put under a nitrogen atmosphere. Phosphoryl chloride (0.118 mL, 1.27 mmol) was added, and the reaction was put in an ice bath and stirred for 25 minutes; the solution turned bright red during stirring. Product pyrrole (0.2 g, 1.08 mmol) was dissolved in DMF (1 mL, 12.97 mmol) and added dropwise to the reaction over five minutes. The reaction was warmed to room temperature. TLC was performed to monitor the reaction by taking a drop of reaction product and adding 3:1 hexanes, NaOH (0.5 mL, 26.63 mmol), and ether (0.5 mL, 4.81 mmol), and then performing TLC on the top extracted layer. Product was poured over ice (20 mL), and NaOH (10%) was added to adjust the pH to 6 and then to 11. The product was stirred for 45 minutes while pH was continuously monitored. The development of crystals was observed. The product was filtered and dried for 10 minutes. Product crystals were dissolved in MeCN (3 mL), swirled, and heated until dissolved. Recrystallization and vacuum filtration yielded a dark brown crystalline solid (0.129 g, 56): Melting point 109.2º C - 111.0º C; FTIR 3333.79, 2920.23, 2738.18, 1648.91, 1532.12, 1514.79; 1H NMR (400 MHz, CDCl3) δ 9.868 (s, 1H), 7.297 (m, 2H), 7.075 (m, 2H), 6.3725 (d, 1H), 2.443 (s, 3H), 2.270 (s, 3H), 1.979 (s, 3H).

Final Product: (Z)-2-((3-phenyl)imino)thiazolidin-4-one (0.1021 g, 0.49 mmol) was dissolved in EtOH (2 ml), and piperidine (0.08 mL, 0.809 mmol) followed by product pyrrole (0.1039 g, 0.488 mmol) were added to the dissolved solution. Solution was incubated for 90 minutes (60º C); crystallization was observed. Product underwent vacuum filtration and was washed with EtOH (4 mL). Final product was a tan crystalline powder (0.0514 g, 27%): Decomposition temperature: 240.3º C; FTIR 3041.29, 2943.76, 2917.61, 2738.94, 1701.25, 1636.69, 1585.99. 1H NMR (400 MHz, CDCl3) δ 7.733, (s, 1H), 7.414 (t, J= 7.8 Hz, 2H), 7.20 (m, 5-6H), 7.041 (d, J= 8 Hz, 2H), 6.114 (s, 1H), 2.429 (s, 3H), 2.130 (s, 3H), 1.973 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 138.720, 135.653, 134.941, 131.696, 130.086, 129.420, 127.631, 126.090, 124.975, 121.777, 115.397, 105.114, 21.185, 12.707, 11.065.

Linked Posts
Attached Files
14th November 2013 @ 18:07

reaction scheme

1-(4-methoxyphenyl)-2,5-dimethyl-1H-pyrrole: p-Anisidine (.614g, 5.0mmol) was combined with 2,5-hexanedione and heated overnight (130°C). Product was dissolved in 2 tube volumes of ether and 2 tube volumes of 10% citric acid. After separation of layers, the organic layer was washed with H2O (10 mL) and NaCL in solution (10 mL). The solution was dried with MgSO4. Filtrate was concentrated under reduced pressure. The resulting solid was dissolved in a minimal (<5 mL) amount of hot ethanol. The solution was allowed to cool and water was added dropwise until the solution became cloudy (4 drops). Solution transferred into ice-cold beaker for further crystallization. Vacuum filtration was used to filter the solution and separate out the product (0.258 g). Melting point of substance was 59.7-59.8 oC. FTIR: 3012, 3004, 2958 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.89-7.86 (m, 2H), 7.77-7.75 (m, 2H), 6.0 (s, 2H), 4.1 (s, 3H), 2.1 (s, 6H).

1-(4-methoxyphenyl)-2,5-dimethyl-1H-pyrrole-3-carbaldehyde: An ice bath was created in which POCl3 (0.144mL, 1.54mmol) and DMF (1.0mL) were added and stirred (25 min). DMF (1.0mL) was added to the above pyrrole (258mg, 1.28mmol). The two solutions were combined dropwise (5 min). Allowed reaction to warm to room temp until reaction was complete (monitored via TLC). Poured reacted material over ice. Added NaOH (approx. 6mL) dropwise (monitored pH with pH paper). The reaction was filtered under vacuum. The solid was allowed to dry overnight and then massed (172mg, 66.6%). Melting Point: 140.1°C to 141.7°C. IR: 3100, 2933, 1650.89, 1513.56 cm-1; 1H-NMR (400MHz, CDCl3) δ 9.867 (s, 1H), 7.26 (s, 1H), 7.10 (d, J= 6.8Hz, 2H), 7.01 (d, J=6.8Hz, 2H), 6.367 (s, 1H), 3.879 (s, 3H), 2.269 (s, 3H), 1.979 (s, 3 H).

Thiazolidinone Pyrrole: (Z)-2-((3-phenyl)imino)thiazolidin-4-one (0.1297 g, 0.675 mmol) was dissolved in ethanol (0.6 mL). Piperidine (0.1 mL, 1.0125 mmol) was added to this solution. The aldehyde synthesized above (0.1548g, 0.675 mmol) was combined with this solution. The solution heated at 60 °C overnight until completion (monitored by TLC). The resulting solid was filtered under vacuum. The resulting brown crystals were the final product (0.1560 g, 59.6%). The melting point was 279.0-279.5 °C. FTIR: 3401, 3093, 3054, 2943, 1628, 1590 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.41, (t, 2H) 7.22 (m, 3H) 7.07 (d, 2H), 6.98 (d, 2H), 6.11 (s, 1H), 3.86 (s, 3H), 2.13 (s, 3H), 1.97 (s, 3H). 

Linked Posts
This post is linked by:
Attached Files
14th November 2013 @ 17:58

reaction scheme

4-(2,5-dimethyl-1H-pyrrol-1-yl)benzenesulfonamide: Sulfanilamide (1.72 g, 10 mmol), 2,5-hexanedione (1.4 mL, 12 mmol) and sulfamic acid (50 mg, 0.5 mmol, 5 mol%) combined in capped tube and heated to 130 °C overnight. Solid recrystallized from hot ethanol to give a beige powder. 1H NMR (400 MHz, CDCl3): 8.04 (d, 2H), 7.37 (d, 2H), 5.93 (s, 2H), 5.25 (br s, 2H), 2.05 (s, 6H). 

4-(3-formyl-2,5-dimethyl-1H-pyrrol-1-yl)benzenesulfonamide: Cold DMF (0.8mL) was stirred in an ice bath under nitrogen atmosphere. Phosphoryl chloride (0.19mL, 1.54mmol, 1.2 equiv.) was added dropwise and reaction was stirred for 25 minutes. A solution of 4-(2,5-dimethyl-1H-pyrrol-1-yl)benzenesulfonamide (0.32g, 1.28 mmol, 1.0 equiv) and DMF (0.8mL) was added dropwise over five minutes, then brought to rt until complete (30 min; monitored with TLC). Poured over ice (16mL) and stirred until melted. Reaction pH was 1. Reaction was neutralized with NaOH (3.4mL, 10%NaOH) until it held a pH of 6. Reaction was filtered using vacuum filtration, and was rinsed with cold clean water; yielded a sandy-brown powder (0.191g). Recrystallization in acetonitrile gave similar brown solid (0.105g, 33%). Melting point: 202.6-206.7°C; IR: peaks not labeled, however, spectra showed benzene ring, carbonyl peak, the presence of single and double carbon-carbon bonds, and amine; 1H NMR (400 MHz, CDCl3): 9.89 (s, 1H), 8.07 (d, 2H), 7.32 (d, 2H), 6.41 (s, 1H), 3.19 (s, 2H), 3.10 (s, 2H), 2.3 (m, 3H), 2.01 (m, 3H).

Knoevenagel Condensation: (Z)-2-((3-phenyl)imino)thiazolidin-4-one (0.078 g, 0.375 mmol) was dissolved in ethanol (7 mL) at rt. Piperidine (0.06 mL, 0.5625 mmol) and 2,5-dimethyl-N-phenyl(4-sulfamine)-pyrrole-3-carbaldehyde (0.10 g, .0375 mmol) were added. Solution refluxed overnight at 60°C and cooled to rt. Vacuum filtration (ethanol) afforded brown solid crystals (0.0696 g, 67%). MP: Decomposed at 250.4°C. IR: 3401, 3094, 3054, 2943, 2744, 1628, 1590, 1537, 1497 cm-1. 1H NMR (400 MHz, CDCl3) δ 9.884 (s, 1H), 8.198-8.016 (m, 2H), 7.284-7.141 (m, 8H), 3.193-3.085 (d, 2H). Spectrum retaken in DMSO-d6 at 50 C (attached), and was much cleaner.

Attached Files
14th November 2013 @ 17:30

reaction scheme

4-(2,5-Dimethyl-1H-pyrrol-yl)benzonitrile: 4-aminobenzonitrile (1.36 g, 10 mmol), 2,5-hexanedione (1.4 mL, 12 mmol) and sulfamic acid (50 mg, 0.5 mmol, 5 mol%) combined in capped tube and heated to 130 °C overnight. Solid recrystallized from hot ethanol to give a tan powder (1.403 g, 63%).

4-(3-Formyl-2,5-dimethyl-1H-pyrrol-1-yl)benzonitrile (FPBC): DMF (0.40 mL) was stirred with phosphoryl chloride (0.14 mL, 1.5 mmol,) at 0 °C under a nitrogen atmosphere. 4-(2,5-Dimethyl-1H-pyrrol-yl)benzonitrile (PBC) (196 mg, 1.0 mmol,) in DMF (0.40 mL) was added dropwise over 5 min. Once the reaction reached completion (20 min, monitored by TLC), the solution was poured over ice (4 mL) and the pH brought to 8 (approx. 10% NaOH). Once fully reacted (30 min) the reaction was filtered and the resulting grey crystal purified with MeCN and filtered affording FPBC (90 mg, 40%) as a brown crystal: FTIR (neat) 3094, 3060, 2956, 2923, 2837, 2755, 2229, 1651, 1603 cm-1; 1HNMR (400 MHz, CDCl3) δ 9.90 (s, 1H), 7.86 (d, 2H, J = 8.4 Hz), 7.36 (d, 2H, J = 8.4 Hz), 6.42 (s, 1H), 2.29 (s, 3H), 2.01 (s, 3H). mp 162.4-163.9.

Nitrile Thiazolidinone Pyrrole (NTP): Dissolved FPBC (72 mg, 0.32 mmol) and (Z)-2-((3-phenyl)imino)thiazolidin-4-one (61 mg, 0.32 mmol) in EtOH (4.8 mL). Piperidine (0.048 mL, 0.48 mmol) was added and the solution heated to 60 °C. Upon reaction completion (90 min) the solution was cooled to room temperature and filtered and the solid precipitate washed with EtOH yielding NTP (57 mg, 49%) as a yellow solid: FTIR (neat) 3066, 2978, 2792, 2232, 1700, 1641, 1600 cm-1; 13C NMR (399 MHz, CDCl3) δ 165.3, 163.3, 141.6, 134.4, 133.3, 131.0, 129.4, 128.9, 126.6, 125.1, 121.9 117.7, 116.5, 112.8, 106.4, 110.5, 12.8, 11.2. mp 315 (dec.) 1H NMR (DMSO-d6, at 60 C, which is much cleaner than that at ambient temperatures -- hindered rotation of aromatic rings?  cis-trans isomerization in the enone or imine?): 11.5 (br s, 1H), 7.99 (d, 2H, J=8.6 Hz), 7.53 (apparent d, 3H), 7.38 (apparent t, 2-3H), 7.15 (apparent t, 2H), 6.10 (s, 1H), 2.10 (s, 3H), 1.97 (s, 3H).

Attached Files
14th November 2013 @ 17:25

reaction scheme

1-(3-methylphenyl)-2,5-dimethylpyrrole: m-Anisidine (5 mmol, 0.57mL) was added to 2,5-hexanedione (4.5 mmol, 0.53mL) and heated to 130ºC overnight. The reaction was combined with ether (10 mL) and citric acid (10 mL) in a separatory funnel, and the organic layer was washed with water (10 mL) followed by sodium chloride (10 mL). The organic layer was then dried over magnesium sulfate (MgSO4) and filtered. Evaporation of the solvent was followed by the addition of methanol (1 mL) and purification by flash chromatography (silica gel, hexanes-ethyl acetate, 8:1) to give the title compound as a yellow oil (350 mg, 35%). 1H NMR (400 MHz, CDCl3) δ 7.338 (t, 1H), 6.943 (dd, 1H), 6.807 (dd, 1H), 6.753 (d, 1H), 5.891 (s, 2H), 3.804 (s, 3H), 2.045 (s, 6H).

1-(3-methylphenyl)-2,5-dimethylpyrrole-3-carboxaldehyde: Phosphoryl chloride (0.192 mL) was added to dimethylformamide (1 mL), stirring on ice and under a nitrogen atmosphere for 25 minutes. Dimethylformamide (1 mL) was added to the crude compound 1; this was added dropwise to the stirring reaction on ice. Using TLC (hexanes-ethyl acetate, 3:1) to monitor, upon completion the reaction was poured over ice. The pH was adjusted to 11 using NaOH (10%), followed by an aqueous workup where the reaction was first combined with NaOH. Ethyl acetate was added to the aqueous layer, and the two organic layers were combined; water was added, and the organic layer was then combined with a saturated brine solution. This was dried over MgSO4 and filtered. The solvent was evaporated under reduced pressure to give compound 2 as a colorless oil (117 mg, 29%). 1H NMR (400 MHz, CDCl3) δ 9.868 (s, 1H), 7.418 (t, 1H), 7.02 (m, 1H), 6.79 (m, 1H), 6.731 (ds, J = 2 Hz, 1H), 6.375 (s, 1H), 3.847 (s, 3H), 2.299 (s, 3H), 2.008 (s, 3H); IR υmax  2921.16, 2837.17, 1734.73, 1654.77 cm-1.

Final Product: (Z)-2-((3-phenyl)imino)thiazolidin-4-one (96 mg) was dissolved in ethanol (2 mL) and piperdine (0.078 mL) was added. This was combined with the aldehyde above (115 mg) and heated to 60ºC. The reaction was monitored using TLC (hexanes-ethyl acetate, 3:1) and after 4.5 hours, the product precipitated out. This was filtered and washed with ethanol to give compound 3 as a tan powder (68 mg, m.p. 251-255°C, 33%). 1H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.40 (m, 3H), 7.8 (m, 3H), 6.99 (m, 1H), 6.75 (m, 1H), 6.69 (t, 1H), 3.83 (s, 3H), 2.16 (s, 3H), 2.00 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.362, 138.665, 135.444, 131.565, 130.179, 129.420, 125.022, 121.808, 120.151, 115.505, 114.321, 113.740, 105.230, 55.519, 12.668, 11.050; IR υmax 2961.47, 2793.77, 1683.33, 1622.90 cm-1.

Attached Files