Abstract
The experiment conducted is a palladium catalyzed coupling of a terminal alkyne to 4-Iodonitrobenzene. 1.25 mL of 95% ethanol was added along with 93mg of 4-Iodonitrobenzene, 80mg piperazine hexahydrate and 4 mg CuI, in a 5mL clean and dry conical vial plus spinvane. 80 µL (density 0.898 g/mL) of tetrahydro-2-(2-propynyloxy)-2H-pyran was added to the solution through an automatic pipette. To this add 3 mg of Pd(OAc)2, refluxed and stirred under a water cooled condenser for half an hour until it turned dark brown. The reaction mixture was then poured into a clean and dry evaporating dish and heated gently with a boiling stone in a steam bath until a dark brown solid was coated on the dish. It was then cooled on a bed of ice for 5 minutes. 1 mL of 4:1 petroleum ether/diethyl ether was added to the mixture using a Pasteus pipette to cool and stirred with the dark solid. The solvent was then evaporated and allowed to cool in ice to facilitate crystallization. After crystallization the crystals were taken, dried and weighed to get a percentage yield of 77.34%. There are two possible conformations that the product could form (1 and 2). 1H NMR data shows that the conformation 1 is the more likely product.
Introduction
Because of the properties of transition metals, they have been widely used in the synthesis of organic molecules. They can not only activate organic compounds, but can also catalyze the formation of new carbon-carbon bonds. The aim of this experiment was to carry out the palladium catalyzed coupling of terminal alkyne to 4-Iodonitrobenzene. Two catalysts are needed for this reaction: a zero-valent palladium complex and a halide salt of copper(I). The palladium complex activates the organic halides by oxidative addition into the carbon-halogen bond. Since hydrogen halides are a byproduct of this reaction, the reaction is usually carried out in a basic medium. The product of this reaction were pale yellow or colorless crystals of 4-Iodonitrobenzene which were separated, dried and weighed for quantitative analysis. Although there are two possible conformations of the product, fig 1, 1H NMR data shows that the conformation 1 is the more likely product.
Reaction
The reaction mechanism has not been understood conclusively, but generally involves two separate cycles; one involving palladium and the other, copper.
The palladium cycle involves the conversion of the Pd(0) catalyst into Pd(II) through an oxidative addition which then reacts with the copper salt produced in the copper cycle. Both the ligands being trans oriented get converted into cis through a cis trans isomerization and the product is finally produced in a reductive elimination with Pd(0) being reproduced.
The copper cycle is not conclusively known with the production of certain intermediates yet to be proven, although indirectly, it is suggested to be involved in the reduction of Pd(II) catalysts to Pd(0).
General Procedure
1.25mL of 95% ethanol was added to a 5mL clean, dry conical vial plus spinvane. 93mg of 4-Iodobenzene was taken in the conical vial and 80mg of piperazine hexahydrate was added to the mixture while stirring. To this, 4mg of CuI was also added. 80µL of tetrahydro-2-(2-propynyloxy)-2H-pyran was added to this through an automatic pipette. 3mg of Pd(OAc)2 was taken in the conical vial and the mixture was refluxed, stirred in the hood under a water cooled condenser for half an hour until it turns brown.
A small evaporating dish was washed and cleaned with water and then acetone and allowed to dry. A 25 ml round-bottomed flask, and a 50 mL beaker were cleaned with water, then acetone and allowed to dry in an oven for about 15 min. they were taken out and allowed to cool before used later in the experiment. After cooling, pour the reaction mixture into the clean and dry evaporating dish. 0.5 mL of 95% ethanol was taken again, the reaction vial rinsed and the washings transferred to the evaporating dish.
A small boiling stone was added to the evaporating dish and heated gently till all the ethanol evaporated. The evaporating dish, which was coated with a dark brown solid, was allowed to cool on a "bed" of ice for at least 5 min. A Pasteur pipette column was prepared using a small cotton plug, 0.5 cm of sand and 2.5 cm of silica gel. The pipette was clamped to a ring stand in a hood and the cool, clean, dry, tared 25mL round-bottomed flask was placed under it. 4:1 petroleum ether/diethyl ether was added to the column to wet it completely. 1 mL of 4:1 petroleum ether/diethyl ether was added to the cool evaporating dish in the hood. The solvent was mixed thoroughly using a microscale spatula. Using a Pasteur pipette, the yellow solvent was transferred to the pipette column. This process was repeated thrice. After adding the last washing, the column was washed with 2-3 mL of 4:1 petroleum ether/diethyl ether.
The solvent was then evaporated and cooled to obtain pale yellow or colorless crystals. After complete crystallization, the crystals were taken out, dried and then weighed to calculate the percentage yield.
Results and Discussions
The percentage yield calculated is 77. 34% which is close to the expected yield of (80-90)%. 1H NMR analysis showed this product to be relatively pure with only minor contaminants.
1H NMR: δ 1.56-1.87 (m, 3H, J = 6.41, 2.29, 8.24, 3.21, 5.95, 3.66, 2.75, 4.12, 17.40, 1.83, 5.50, 1.83), δ 2.39-2.41 (dd, 1H, J = 2.29), δ 3.55-3.59 (m, 1H, J = 1.83, 2.29, 1.37, 2.75, 0.92, 3.21, 4.12), δ 3.85-3.91 (m, 1H, J = 3.21), δ 4.24-4.25 (m, 1H, J = 2.29, 1.83), δ 4.27-4.28 (m, 1H, J = 2.29), δ 4.31-4.32 (m, 1H, J = 2.75, 2.29), δ 4.45-4.47 (s, 1H, J = 16.03), δ 4.47-4.49 (s, 1H, J = 16.03, 13.28). δ 4.52-4.54 (s, 1H, J = 13.28, 16.03), δ 4.54-4.56 (s, 1H, J = 16.03), δ 4.80-4.83 (m, 1H), δ 4.86-4.88 (m, 1H, J = 3.21, 3.66), δ 7.57-7.59 (m, 3H, J = 7.33), δ 8.16-8.18 (m, 3H, J = 7.33).
Discussions
General Considerations: All of the reagents and solvents used in this reaction were bought from chemical vendors and were used without any attempt to further purify them.
Concentration of reactions mixtures was carried out using a rotary evaporator at 72 °C. The spectral data for this experiment was obtained using a JEOL 400 MHz NMR spectrometer. The, NMR spectral data was collected at ambient temperatures. 1H spectra were obtained at 400 MHz in acetone-d. δ values are reported in parts per million (ppm) and referenced against chloroform-d (7.25 ppm for 1H), and J coupling values are reported in Hz.
Besides this, there are a number of precautions that need to be taken while carrying out this experiment. 4-Iodonitrobenzene being corrosive, should be handled carefully without any skin contact. The chemical tetrahydro-2-(2-propynyloxy)-2H-pyran is a severe irritant and should always be kept under the hood. Pd(OAc)2 being expensive, must be used sparingly. If rotator evaporators are available, the tedious jobs of cleaning the evaporating dish, the 25mL round bottom flask and the 50mL beaker as well as evaporating the solvent can be spared. There should be no flames in the labs as most of the chemicals are highly inflammable. During the cooling processes involving ice, ice should strictly be kept out the dish.
Conclusion
The reaction involving palladium coupling of a terminal alkyne to 4-Iodobenzene was successfully carried out and the yield obtained was 77.34%. The spectral data confirmed the relative purity of the product with the presence of only minor contaminants. 1H NMR analysis showed that out of the two possible conformations of the product, conformation 1 (fig 1) was the most abundant.
References cited
Li-Ping, Chen & Hui-Ping, Chen, “DFT Investigation on the Mechanism of Pd(0) Catalyzed Sonogashira Coupling Reaction” Chinese J. Struct. Chem, Vol. 30, No. 9(2011), 1289-1297.
