Metody Laboratoryjne Laboratorium ChOrg2 Prowadzący: mgr Elżbieta Gońka, mgr Damian Myśliwiec

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1 Metody Laboratoryjne Laboratorium ChOrg2 Prowadzący: mgr Elżbieta Gońka, mgr Damian Myśliwiec 1) itrowanie 4,4'-Dibromo-2-nitrobifenyl. Do trójszyjnej kolby o pojemności 750 ml, zaopatrzonej w rdzeń magnetyczny, chłodnicę zwrotną z odprowadzeniem gazów, termometr i wkraplacz wprowadza się 4,4'-dibromobifenyl (0.064 mol, 20 g) oraz 300 ml lodowatego kwasu octowego. Zawartość kolby ogrzewa się na łaźni olejowej do 100 C. W osobnym naczyniu o poj 250 ml sporządza się roztwór 92.5 ml dymiącego kwasu azotowego, oraz 7.5 ml wody. Zawartość naczynia przenosi się do wkraplacza i powoli wkrapla do gorącego roztworu w kolbie, tak aby wydzielające się w reakcji tlenki azotu, nie opuszczały chłodnicy zwrotnej. Po dodaniu całej ilości kwasu, roztwór miesza się przez 1 h. Po tym czasie roztwór przelewa się do dużej zlewki i chłodzi w łaźni z lodem w celu wytrącenia produktu. Wytrącony osad oddziela się na lejku Schotta, przesącz należy zachować w celu wydzielenia kolejnej porcji produktu. Osady przemywa się na lejku kilkoma porcjami wody a następnie mrożonym etanolem. Produkt suszy się pod próżnią do następnego dnia. 2) Reakcja Cadogana (synteza 2,7-dibromokarbazolu) A solution of 4,4'-dibromo-2-nitrobiphenyl (1.19 g, 5.98 mmol) and PPh 3 (3.92 g, mmol) in o-dcb (12 ml) was heated to reflux with vigorous stirring for 21 h, during which time the color changed from yellow to brown. At that time, reaction was cooled to room temperature and concentrated under high vacuum. The crude product was purified by column chromatography (silica gel, 30 % dichlorometane in hexanes) or flash chromatography (silica gel, 5% DCM in hexanes). Podział surowej mieszaniny po syntezie 2,7-dibromokarbazolu. 4) Formylowanie 9-Butyl-9-carbazole-2,7-dicarbaldehyde (S3). In a round bottomed flask equipped with a stirring bar, compound 2,7-dibromo-9-butyl-9-carbazole OC CO (15.03 g, mmol) was dissolved in dry tetrahydrofuran (400 ml) under Bu a nitrogen atmosphere. After cooling to 78 C with an acetone liquid nitrogen bath, n-butyllithium (2.5 M solution in tetrahydrofuran, 157 mmol, 63 ml) was added to the solution, resulting in the formation of a white slurry. The mixture was stirred under nitrogen for 30 min. and,-dimethylformamide (30.5 ml, 394 mmol) was added. The reaction mixture was allowed to warm to room temperature and was stirred for additional 2 h. The mixture was diluted with water and extracted with dichloromethane. Organic extracts were dried over anhydrous magnesium sulfate and filtered, and the solvent was removed on a rotary evaporator. The crude product was purified by column chromatography (silicagel, 50% dichloromethane in hexanes). The second fraction was collected and concentrated on a rotary evaporator to yield yellow crystals (11.02 g, 91%). 1 MR(500 Mz, chloroform d, 300 K): δ (s, 2), 8.27 (d, 2 4 J = 8.01 z), 7.99 (s, 2), 7.78 dd, 1

2 2, 3 J = 8.0 z, 4 J = 1.2 z), 4.43 (t, 2, 3 J = 7.2 z) 1.90 (m, 2), 1.42 (m, 2), 0.96 (t, 3, 3 J = 7.12 z). 13 C MR (125 Mz, chloroform-d, 300K): δ , , , , , , , 43.47, 31.25, 20.57, ) Reakcja McMurry ego In a 250 ml three-necked round-bottomed flask with a reflux condenser and a septum were placed zinc powder (748 mg, mmol) and copper(i) chloride (69 mg, 0.36 mmol). The apparatus was filled with argon and oxygen-free tetrahydrofuran (10 ml) was introduced through a Bu Bu Bu syringe. Titanium tetrachloride (0.6 ml, 5.72 mmol) was added dropwise over 2 minutes using a syringe. The mixture was then heated under reflux for 3 h. Subsequently, a solution of 3,6-dibromo-9-butyl-9-carbazole- 2,7-dicarbaldehyde (100 mg, 0.22 mmol) in oxygen-free tetrahydrofuran (20 ml) was slowly added to the boiling mixture using a syringe. After completion of the addition (2 h), the septum was replaced with a glass stopper and the reaction mixture was kept under reflux for 12 h. After that time, the mixture was cooled down to room temperature. Aqueuous ammonia (6%, 100 ml) was added. The mixture was extracted with dichloromethane. The organic layer was washed with brine, dried over a 2 SO 4, and evaporated to give an yellow-orange oil. The crude product was purified by column chromatography (silica gel, dichloromethane hexanes = 1:1). and then by preparative TLC. After filtration, solvents were removed under reduced pressure to give the product as a yellow solid (7.1 mg, 7.6%). 1 MR (600 Mz, chloroform d, 300 K): δ 8.05 (s, 6), 7.00 (s, 6), 6.88 (s, 6), 3.43 (t, 6, 3 J = 7.3 z), 0.87 (m, 6), 0.57 (m, 6), 0.17 (t, 9, 3 J = 7.3 z). 13 C MR (151 Mz, chloroform-d, 300K): δ , , , , , , , 42.49, 30.22, 19.84, R-MS (MALDI): m/z [M, major peak], calcd. for C : ) Reakcja Williamsona OC 4 9 O 4-Butoxybenzaldehyde. In a 1 L round bottomed flask equipped with a reflux condenser and a magnetic stirring bar were dissolved 4-hydroxybenzaldehyde (35 g, 287 mmol) and 1-bromobutane (30.92 ml, 287 mmol) in,-dimethylformamide (750 ml). The mixture then was stirred under nitrogen for 20 minutes. Anhydrous potassium carbonate ( g, 860 mmol) was then added and the mixture was stirred and heated at 60 C under nitrogen. After 20 h, the reaction was allowed to cool to room temperature, treated with excess water, and extracted with dichloromethane. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure yielding a brown oil (49.8 g, 97%). 2

3 1 MR (600 Mz, chloroform-d, 300 K): δ 9.85 (s, 1), 7.80 (d, 2, 3 J = 8.8 z), 6.96 (d, 2, 3 J = 8.8 z), 4.02 (t, 2, 3 J = 6.5 z), 1.78 (m, 2), 1.48 (m, 2), 0.96 (t, 3, 3 J = 7.4 z). 7) Reakcja Knoevenagela General procedure for the synthesis of diarylacrylonitriles (cyanostilbenes). Aldehyde (1 equiv.) and the corresponding acetonitrile (1 equiv.) were placed in a round bottomed flask equipped with a magnetic stirring bar. Absolute ethyl alcohol (5 ml/mmol of aldehyde) was added followed by an ethanolic solution of sodium ethoxide (1 M, ca. 1 ml/mmol of aldehyde). The mixture was refluxed for 2 h, changing color to yellow. Towards the end of the reaction a yellow precipitate was usually formed. After cooling the reaction mixture to room temperature, the precipitate was filtered, washed with ethanol and dried. The product usually contained the pure Z isomer. C 4 9 O OC 4 9 C 2,3-Bis-(4-butoxyphenyl)acrylonitrile. The mixture of 4-hydroxybenzaldehyde and 2-(4- butoxyphenyl)aceonitryle was refluxed for 3 h and cooled to room temperature. The resulting precipitate was filtered, washed with ethanol and dried, yielding yellow crystals (42.1 g, 94%). 1 MR (500 Mz, chloroform-d, 300 K): δ 7.81 (d, 2, 3 J = 8.5 z), 7.54 (d, 2, 3 J = 9.0 z), 7.32 (s, 1), 6.92 (m, 4), 3.99 (m, 4), 1.77 (m, 4), 1.49 (m, 4), 0.97 (m, 6). 8) Reakcja Zarda-Bartona General procedure for the synthesis of ethyl 4 diarylpyrrole 2 carboxylates. In a dry flask equipped with magnetic stirring, an appropriate cyanostilbene was dissolved in dry tetrahydrofuran and purged with argon for 1h. ext, ethyl isocyanoacetate (1 equiv.) was added. The mixture was cooled to 0 C and a solution of potassium tert butoxide (1 M in tetrahydrofuran) was added. The mixture was stirred under argon until thin layer chromatography showed complete consumption of the starting material. The mixture was diluted with water and extracted with dichloromethane. Combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the solvents were removed on a rotary evaporator. The product was purified by column chromatography (silica gel, dichloromethane). The second fraction was collected, characterized by blue fluorescence under UV light. The solvent was removed on a rotary evaporator, to yield the product as a yellow orange solid. 3 CO OC 3 COOEt Ethyl 3,4-bis(4-methoxyphenyl)-1-pyrrole-2-carboxylate) was obtained in 88% yield (3.93 g) on a 11.2 mmol scale. 3

4 1 MR (500 Mz, chloroform-d, 300 K): δ 9.19 (s, 1), 7.16 (d, 2, 3 J = 8.3 z), 7.00 (m, 3), 6.80 (d, 2, 3 J = 9.2 z), 6.72 (d, 2, 3 J = 9.2 z), 4.17 (q, 2, 3 J = 7.0 z), 3.78 (s, 3), 3.73 (s, 2), 1.16 (m, 3, 3 J = 7.1 z). C 4 9 O OC 4 9 COOEt Ethyl 3,4-bis(4-butoxyphenyl)-1-pyrrole-2-carboxylate) was obtained in 98% yield (6.3 g) on a 14.7 mmol scale. 1 MR (500 Mz, chloroform-d, 300 K): δ 9.08 (b, 1), 7.15 (d, 2, 3 J = 8.9 z), 7.00 (m, 3), 6.80 (d, 2, 3 J = 8.9 z), 6.72 (d, 2, 3 J = 8.9 z), 4.18 (q, 2, 3 J = 7.1 z), 3.95 (t, 2, 3 J = 6.6 z), 3.89 (t, 2, 3 J = 6.5 z), 1.73 (m, 4), 1.47 (m, 4),1.17 (t, 3, 3 J = 7.1 z), 0.96 (m, 3, 3 J = 7.3 z), 0.94 (t, 3, 3 J = 7.3 z). C O OC COOEt Ethyl 3,4-bis(4-dodecyloxyphenyl)-1-pyrrole-2-carboxylate) was obtained in 35% yield (1.28 g) on a 5.23 mmol scale. 1 MR (500 Mz, chloroform-d, 300 K): δ 9.19 (s, 1), 7.13 (d, 2, 3 J = 8.80 z), 6.98 (m, 3), 6.78 (d, 2, 3 J = 8.7 z), 6.70 (d, 2, 3 J = 8.9 z), 4.16 (q, 2, 3 J = 7.1 z), 3.92 (t, 2, 3 J = 6.6 z), 3.86 (t, 2, 3 J = 6.5 z), 1.73 (m, 4), 1.40 (m, 4),1.25 (m, 16), 1.15 (m, 3, 3 J = 7.1 z), 0.85 (m, 6). 9) Dekarboksylacja General procedure for the synthesis 4-aryl-1-pyrrole Ethyl 4 diarylpyrrole 2 carboxylates (1 equiv), potassium hydroxide (2 equiv) and ethylene glycol (2.50 ml/mmol) were placed in a 50 ml round bottomed flask equipped with a magnetic stirring bar. The mixture was purged with nitrogen for 1 h. The mixture was heated to 190 C and stirred under nitrogen for 3 h. Subsequently, the mixture was allowed to cool to room temperature, treated with excess water and brine, and extracted with dichloromethane. The combined organic extracts were dried over sodium sulfate, filtered and evaporated under reduced pressure, yielding yellow crystals. 3 CO OC 3 3,4-Bis(4-methoxyphenyl)-1-pyrrole was obtained in 91% yield (2.644 g) on a 9.6 mmol scale. 1 MR (600 Mz, chloroform-d, 300 K): δ 8.19 (b, 1), 7.17 (d, 4, 3 J = 8.8 z), 6.83 (d, 2, 4 J = 3.0 z), 6.79 (d, 4, 3 J = 8.7 z), 3.78 (s, 6). 4

5 C 4 9 O OC 4 9 3,4-Bis(4-butoxyphenyl)-1-pyrrole was obtained in 90% yield (3.1 g) on a 15.6 mmol scale. 1 MR (600 Mz, chloroform-d, 300 K): δ 8.18 (b, 1), 7.16 (d, 4, 3 J = 8.8 z), 6.83 (d, 2, 4 J = 2.6 z), 6.78 (d, 4, 3 J = 8.8 z), 3.92 (t, 4, 3 J = 6.4 z), 1.74 (m, 4), 1.47 (m, 4), 0.95 (t, 6, 3 J = 7.4 z). C O OC ,4-Bis(4-butoxyphenyl)-1-pyrrole was obtained in 95% yield (1.43 g) on a 2.69 mmol scale. 1 MR (600 Mz, chloroform-d, 300 K): δ 8.25 (s, 1), 7.15 (d, 4, 3 J = 8.8 z), 6.81 (d, 2, 4 J = 2.6 z), 6.77 (d, 4, 3 J = 8.7 z), 3.90 (m, 4, 3 J = 6.5 z), 1.74 (m, 4), 1.42 (m, 4), 1.27 (m, 16), 0.95 (t, 6, 3 J = 7.4 z). Cl Cl 3,4-bis(4-chlorophenyl)-1-pyrrole was obtained in 95% yield (1.43 g) on a 2.69 mmol scale. 1 MR (600 Mz, chloroform-d, 300 K): δ 8.31 (s, 1), 7.21 (d, 4, 3 J = 8.7 z), 7.14 (d, 4, 3 J = 8.9 z), 6.88 (s, 1), 6.87 (s, 1). 3,6-Dibromophenanthrene. A solution of 4,4 -dibromostilbene (0.250 g, 1.11 mmol), iodine (0.309 g, 1.22 mmol, 1.1 eq.), TF (1.6 g, 1.8 ml, 22.2 mmol) and toluene (1.2 L) was irradiated using a 125W MPV lamp for 36 h/monitored by tlc. After the reaction was over, the excess of iodine was removed by washing the solution with aqueous a 2 S 2 O 3, followed by distilled water. The organic layer was concentrated under the reduced pressure. The pure product was obtained in 97% yield (0.241 g) on a 0.81 mmol scale. It was purified by column chromatography on silica gel using petroleum ether as eluent to afford colorless solid. 1 MR (400 Mz, CDCl3): δ (d, J = 1.56 z, 2), (d, J = 8.48 z, 2), (m, with overlapping d, J = 8.48 z, 4 ). 5

6 11) -alklilowanie In a round bottomed flask equipped with a stirring bar, compound 2,7-dibromo--carbazole (3.0 g, 9.23 mmol), tetraethylammonium perchlorate ( mg, 0.4 mmol) was dissolved in 2-butanone (20 ml). The mixture was stirred under nitrogen for 2 min. and ao (740 mg, 185 mmol) was added. The mixture was heated under a protective atmosphere and left to reflux overnight. Subsequently the reaction mixture was cooled down to room temperature and poured into 100 ml water. The precipitate white solid was filtered off and washed with cold methanol. 6

7 Metody Laboratoryjne Laboratorium ChOrg2 Prowadzący: mgr Elżbieta Gońka, mgr Damian Myśliwiec Poniedziałek (12 15:45) 6 spotkań po 5 h Wtorek (10 11:30) ok. 6 spotkań 2 h Osoba A Osoba B Osoba C Osoba D 1) itrowanie 6) Reakcja Williamsona 8) Reakcja Zarda-Bartona 2) Reakcja Cadogana (synteza 2,7- dibromokarbazolu) 5) Reakcja McMurry ego 8) Reakcja Zarda-Bartona 8) Reakcja Zarda-Bartona 7) Reakcja Knoevenagela 9) Dekarboksylacja 9) Dekarboksylacja 11) -alklilowanie 5) Reakcja McMurry ego 5) Reakcja McMurry ego 6) Reakcja Williamsona 1) itrowanie 8) Reakcja Zarda-Bartona 4) Formylowanie 5) Reakcja McMurry ego 7) Reakcja Knoevenagela 9) Dekarboksylacja 7