A persulfate-promoted metal-free benzannulation of α,β-unsaturated compounds and alkynes in water toward the synthesis of unprecedented polyfunctionalized benzenes is reported.
This is a very simple experimental setup in line with organic chemistry requirements to obtain a range of viable polyfunctionalized benzenes. The main advantage of this technique is the use of water as a solvent which allows the easy isolation of the crude mixture and contributes to the sustainable practice of organic chemistry. Demonstrating the procedure will be Dr.Gabriela Souza, an associate researcher from my laboratory.
To begin, add two milliliters of distilled water to a 15 milliliter test tube containing a stir bar. Sequentially, add 220 microliters of phenol acetylene, 96.8 microliters of 2-cyclohexene-1-one, and 1.5 milliliters of freshly prepared 1.3 molar ammonium persulfate. Cap the tube using a rubber septum and insert a needle in it to avoid eventual pressure buildup during the heating.
Place the tube in an aluminum heating block on a hot plate and heat it at 85 degrees Celsius under vigorous stirring at 1, 150 RPM for eight hours. To allow the progress of the reaction, take a 50 microliter aliquot of the reaction medium and transfer it to a 1.5 milliliter conical vial. Add 50 microliters of ethyl acetate to the vial and shake it.
Then collect the organic top layer with a capillary tube and apply it on a TLC silica-coated glass plate. Dip the plate in a solution of 92:8 hexanes ethyl acetate to analyze. Cool the reaction mixture to room temperature and add one milliliter of ethyl acetate to the test tube.
Stir the suspension for approximately one minute and then centrifuge the suspension at 2, 336 times g at room temperature for one minute. Remove the organic top layer using a Pasteur pipette and transfer it into a round bottom flask. Repeat the addition of ethyl acetate to centrifuging and the removal of the top layer two additional times.
Concentrate the top layer under reduced pressure using a rotary evaporator to obtain a crude oil. Add 55 milliliters of a mixture of hexanes and ethyl acetate at the ratio of 92:8 into a beaker containing 7.5 grams of silicon dioxide. Stir the flask to obtain a homogenous slurry.
Transfer the slurry to a column with 40 millimeter internal diameter to pack the column. Dissolve the crude oil in a minimal amount of ethyl acetate and then transfer this solution to the column. Collect the column effluent in test tubes.
Perform TLC and obtain the desired pure product according to the TLC result showing only one migrating compound. Concentrate the desired solution under reduced pressure on a rotary evaporator and remove the final volatiles under high vacuum for at least one hour. Analyze the sample of the purified product by proton and carbon-13 NMR using deuterated chloroform.
In this protocol, polysubstituted benzene was isolated as a colorless oil. The structure and purity were assessed in the proton and carbon-13 NMR spectra. Peaks for the aromatic protons on the central benzene ring at 8.37 and 7.72 PPM were used as diagnostic signals for the formation of the product.
It is very important to carefully control the temperature of the reaction medium and to ensure a proper stirring of the suspension during the reaction. This procedure can be employed in any other transformation performed in water. Keeping the workup step is an efficient way to obtain a crude mixture from the reaction medium.
This procedure offers an easy and efficient way to study water as a reaction medium and to encourage the design of more sustainable transformations. For operational safety, after capping the tube with a rubber septum, be sure to insert a needle before going to heating. It avoids any pressure buildup during the reaction.
