Preparation of a Corannulene-functionalized Hexahelicene by Copper(I)-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

Here, we present a protocol to synthesize a complex organic compound comprised of three nonplanar polyaromatic units, assembled easily with reasonable yields.

Transcript

The overall goal of this protocol is to synthesize a corannulene functionalized hexahelicene, a complex organic compound comprised of three nonplanar polyaromatic units assembled by click chemistry. The method consists of a set of six reactions steps in a synthesis by using several common organic procedures. Such as free radical reactions, carbon carbon coupling, or click chemistry.

The main advantage of this method is that with subtle modification of these well known reactions, it is possible to achieve similar results for a nonplanar polyaromatic compounds. This method can provide insight into the chemistry of this special family. Because its behavior is not so similar to that of planar aromatic compounds it can also be applied to systems such as extended tetrathiafulvalene or 7 annulene.

We first had an idea for this protocol on our work dealing with host guest recognition when trying to assemble two chorionic units into helicine scaffold. To begin the debromination weigh o. 356g of 2, 15 dimethylhexyl helicene, 374g of freshly recrystallized n bromosuccinimide and 24mg of benzoyl peroxide.

Place all solids in a 100ml schlenk flask with a magnetic stir bar. Put the solids under nitrogen atmosphere by three cycles of gas evacuation followed by refilling with inert gas in the schlenk line. Then add 21ml of carbon tetrachloride.

Degas the solution by the same evacuation and refilling process with vigorous stirring. Take care to prevent massive loss of the solvent. Reflux the mixture at 77 degrees Celsius, using an oil bath for four hours.

The reaction can be followed by proton nuclear magnetic resonance or NMR spectroscopy. Doublets between 3.7 parts per million and 4.0 parts per million should appear indicating the presence of diastereotopic methylene groups. Once finished, cool the mixture to room temperature and remove the solvent under vacuum.

Set up a trap filled with liquid nitrogen to avoid pump contamination. Redissolve the crude in 30ml of dichloromethane. Then transfer the solution to a round bottom flask and mix with 4g of silica gel.

Concentrate the mixture in a rotary evaporator. In the meantime, fill a column with silica gel mixed previously with hexane ethyl acetate as the mobile phase. Add the mixture to the top of the column and then add a 2cm layer of sand.

Carefully pour in the new mobile phase. Perform the chromatography by collecting fractions in test tubes at 20ml per tube and 4ml per tube near the expected product solution. Check the fractions by thin layer chromatography with the same mobile phase and image under ultra violet light.

The expected product should elute at a retention factor of 0.35 as a yellow oil after combining all the desired fractions and removing the solvent in the rotary evaporator. To perform the synthesis, weigh 0.103g of 2, 15 bis bromomethyl hexahelicene and 0.390g of sodium azide. Place both solids in a 50ml schlenk flask equipped with a magnetic stir bar and put under a nitrogen atmosphere.

Then mix 8.6ml of tetrahydrofuran with 5.2ml of water and pour the mixture of solvents into the schlenk flask. After degassing the solution, reflux at 65 degrees Celsius for three hours. Check the reaction by proton NMR.

Methylene group signals should shift to 3.75 parts per million. Afterwards cool down the mixture to room temperature and remove the tetrahydrofuran under a vacuum. Then dilute the sample with 50ml of water.

Tranfser the mixture to separatory funnel and extract three times with 40ml of dicholoromethane. Combine all organic phases and wash with 50ml of distilled water. Purify the crude by column chromatography on silica gel using hexane ethylacetate as the mobile phase to give a yellow oil at a retention factor of 0.38.

Corresponding to 2, 15 bis asomethylhexahelicine. 70mg should be obtained, which corresponds to a yield of 80%At this point in the procedure, there are three additional steps to obtain a ethinyl carnoline. The reactions involve a microwave assisted electrophilic aromatic substitution followed by sonogashira coupling and a subsequent deep protection.

All these procedures are detailed in the text protocol. Weigh 15.3mg of two 15 bis asomethylhexahelicine, 20.0mg of ethinyl carnoline, 1.4mg of ascorbic acid sodium salt and 1.7mg of copper two sulfate pentahydrate. Place all solids in a 50ml schlenk flask equipped with a magnetic bar and put under a nitrogen atmosphere.

A very critical step is to degas the mixture of solvents thoroughly. Mix 3ml of water and 12ml of tetrahydrofuran and pour the mixture into the schlenk flask. Degas the solution thoroughly.

A second important point is to check the reaction periodically to ensure good solvent volume and temperature. Otherwise the reaction may require a longer time ethynil composition. Heat at 65 degrees Celsius for three days with a condensor connected to the top of the flask.

Check the reaction periodically to control temperature, stirring and solvent volume. Check the reaction by proton NMR. The signal at 3.48 parts per million should disappear and be shifted to 7.27 parts per million indicating the consumption of ethinyl carnoline and the existence of the triazol unit.

When finished, remove the tetrahydrofuran under vacuum and dilute with 20ml of water. Transferring the mixture to a separatory funnel and rinsing the flask with 20ml of dichloromethane. After extracting the mixture three times with dicholormethane, combine all organic phases in a round bottom flask and concentrate in a rotary evaporator.

Purify the crude by column chromatography on silica gel eluting with hexane ethyl acetate to get the pale yellow solid at a retention factor of 0.59.27mg should be obtained corresponding to yield of 75%Carnoline and 2, 15 dimethylhexahelicine can be prepared following current methods in a straightforward fashion with very good yields. Both reaction pathways share a common molecule. 2, 7 dimethylnaphthalene as the starting material.

According to the present synthetic route, the final compound was prepared within six steps from the molecules mentioned, giving rise to a divergent to convergent synthesis. Final assembly relies on the famous strategy of copper 1 catalyzed azide alkine cyclo addition known as the click reaction. Following this procedure, a complex organic molecule capable of establishing super molecular interactions with fullerenes can be prepared in reasonable times and with good yeilds.

After watching this video you should have a good understanding of how to apply successfully known reactions in traditional organic chemistry to build a multi step view towards complex non planar poly aromatic molecules with interesting properties.

Journal (Chemistry)

Journal (Chemistry)

Preparation of a Corannulene-functionalized Hexahelicene by Copper(I)-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units

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