Synthesis of Methylated Bucky Bowls by HF elimination

Wissenschaftlicher Aufsatz, 2015

14 Seiten


Table of Contents


Results and Discussion

Summary and Outlook

Experimental Section



For the simulation of complex systems in chemistry or physics the need of very powerful computers grew more and more important over the last decades. As electronic circuits became smaller over the years, more efficient microchips could be fabricated. But the ‘classic’ electronics are limited and therefore new methods had to be developed, like organic electronics. Here, organic molecules are placed between electrodes in order to perform the basic operations known from digital electronics.1,2 The basic idea is, to use a optically switchable single molecular core connected to the electrodes on each side.3 Upon irradiation, most of the applied molecules undergo a conformational change from an open, linear form to a closed ring creating a conjugated π-system throughout the molecule. The π-system enables current flow comparable to a normal wire. The core molecules often consist of dithienylcyclopentenes4 or difurylcyclopentenes5,6, coupled to metal electrodes through anchoring groups. The most prominent anchoring groups are thiol7, amino8 and pyridyl9. Although, this conformational change works well, they exhibit a poor over all conductance due to non-uniform binding geometries10, metal-molecule coupling disturbing the molecular orbitals, or decoupled electron systems.11 In order to overcome this drawbacks, direct molecule-metal coupling12 or Au-C σ-bonds13 are desirable. Molecule-metal coupling was used in the application of fullerenes as anchor molecules. The fullerenes bear the advantage of an enlarged π-system, but suffer from low conductance, potentially based on the weak molecule-metal coupling or intramolecular tunnelling barriers.12 The π-system of a fullerene is not in conjugation with the core molecule because of the unfavourable geometry. Additionally, the coupling of the core molecule leads to a change in the hybridization state of one carbon atom from sp2 to sp3, breaking down the π-system. To elude the weak molecule-metal coupling, the anchoring molecule is bond covalently to the gold surface. Au-C σ-bonds are up to two orders of magnitude more efficient than the previously reported anchoring groups.13 But, this single-molecule junctions don’t exhibit such an amplified π-system. To combine these two systems, an Au-C σ-bond is needed, as well as an enlarged π-system within the anchor molecule, avoiding the hybridisation problem. Therefore bowl-shaped fragments of the fullerenes, so called ‘bucky-bowls’, were deployed. They don’t suffer from a breakdown of the π-system, while being bound to the molecular core.

Here a short route towards the synthesis of a methylated bucky-ball is reported according to previous stated synthesis.14,15 The synthesis comprises a sequence of a Wittig-Horner reaction, followed by a photocyclization. Bromination provides the starting material for a second Wittig-Horner reaction with following photocyclization. The key step of the synthesis is the cove-region closure process (CRC) facilitated by regiospecific HF elimination, promoted through activated aluminium oxide. The final product exhibits the characteristic bowl-like shape. Different reaction conditions were applied for the key step in order to increase the yield and minimize the amount of side products.

Results and Discussion

illustration not visible in this excerpt

Figure 1 Overview of the reaction cascade leading to the substituted bucky-bowl (9)

The synthesis was started with 2-(bromomethyl)-1,4-difluorobenzene (1) and triphenyl phosphane to give the corresponding phosphonium salt. This was reacted in the next step with methyl-2-naphthylketone in a Wittig-Horner reaction, to give a E/Z-mixture of the benzo-stilbene (3) as white crystals and a yield of 72 %. Mainly the E -isomere was formed due to the highly stabilized phosphonium salt. The stilbene was used for the next step without separation and then converted to the substituted benzo[c]phenanthrene (4) using the photocyclization method as described in the literature.14 Iodine acts as an oxidant and leads to recovery of the aromatic system. Propylene oxide binds the resulting HI. Therefore different conditions were applied in order to accelerate the reaction and to improve the yield. The fixed parameters were the benzo[c]phenanthrene derivate (1 eq) and the amount of iodine (1.05 eq). For propylene oxide a lot of different amounts used are stated in the literature. An excess (10 eq) led to a yield of 59 % and a reaction time of 60h. The lack of propylene oxide in the G-Protein gekoppelte Rezeptoren (GPCR) sind die größte Klasse von Membranprote-inen im menschlichen Genom und eine wichtige Targetklasse für derzeitige Medika-mente.

Sie folgen alle demselben strukturellen Aufbauprinzip aus sieben transmembranären α-Helices (TM), die über drei intrazelluläre und drei extrazelluläre Schleifen (ICL und ECL) miteinander verbunden sind. Bei Aktivierung durch einen endogenen oder exogenen Liganden wird eine Signalkaskade induziert, an deren erster Stelle das tri-mere G-Protein steht.

Dieses koppelt an den ICL 3, wird gespalten und migriert ent-lang der Innenseite der Membran zum Effektorsystem.

Eine interessante Gruppe sind die muskarinergen Acetylcholin Rezeptoren (mAChR), die namentlich von deren endogenen Liganden Acetylcholin und vom exogenen A-gonisten Muscarin abgeleitet sind. Neben der Expression im ZNS ist deren Präsenz im pullmonalen System von großem Interesse. Sie werden mit Atemwegserkrankun-gen, wie der chronisch obstruktive Lungenerkrankungen (COPD) und Asthma in Verbindung gebracht.

Diese Rezeptoren können in die Subklassen M1-M5 unterteilt werden. M1, M3 und M5 sind Gq/11 und M2, M4 sind Gi/o gekoppelt. Von den in menschlichen Atemwegen ex-primierten Rezeptoren M1-M4, ist der M3-Rezeptor hauptsächlich auf den glatten Muskelzellen zu finden und stellt das Haupttarget für Medikamente dar. Ziel ist es, in der Therapie von COPD selektiv den Subtyp M3 zu blockieren, um eine Bronchial-verengung zu vermeiden. Simultanes Blockieren des präsynaptischen M2-Rezeptors führt zu einer abgeschwächten Wirkung[6], da dieser ein Autorezeptor ist.was around 99 %, and the yield was 60 % after the work up and purification. The E -isomere is converted into the Z -isomere upon irradiation and is then cyclized. The conversion form E to Z is a slow process and the rate limiting step. Using a less stabilized phosphonium salt, the formation of the Z-isomer can be facilitated. This might lead to shorter reaction times for the photocyclization.

Compound (4) was brominated with NBS (yield = 82 %) to get the starting material (5) for the next Wittig-Horner reaction. Again, a phosphonium salt is formed, applying the conditions described above, but reducing the reaction time to 4.5 h. Using p-tolualdehyde as reagent, a mixture of E/Z methyl substituted styrylbenzo[c]phenanthrene (7) was obtained. The methyl group can be used later on for the coupling of the switch molecule to the bucky-bowl anchor or for extending the bucky-bowl structure. In order to get different binding patterns m-tolualdehyde and o-tolualdehyde might be used as well. The reaction exhibited high E-isomer supremacy based on the stabilized phosphonium salt. Compound (7) was submitted to the second photocyclization, leading to the methylbenzo[s]picene derivative (8). The yields of the reaction were low and the reaction time long, making this step limiting for the whole sequence. The yields might be improved and the time decreased by using a less stabilized phosphonium salt for the Wittig-Horner reaction, in order to obtain mainly the Z-isomere of compound (7). Using flash chromatography it is possible to separate the stilbene from the methylbenzo[s]picene.

As mentioned before, the key step of the synthesis route is the cove-region closure process (CRC) promoted by activated aluminium oxide via HF elimination, leading to methyl substituted indacenopicene (9). The most probable mechanism of the CRC reaction15 is depicted in Figure 2.

illustration not visible in this excerpt

Figure 2 Most potential mechanism of the CRC showing the key points of the process: coordination of the aluminium oxide surface, aromatic transition state, Al-F bond formation.

The formation of the new ring takes place in a concerted fashion and proceeds via a cyclic transition state. The transition state might comprises an aromatic six-membered ring, resulting in a low activation energy. The driving force of the reaction is the formation of a very strong Al-F bond. Yet there is no protocol established for a substituted indacenopicene defining suitable reaction conditions, different conditions were applied based on the literature.15 The basic procedure was developed in the own research group and consists of the activation of γ-Al2O3 at 400-500 °C in a tube, whilst bubbling nitrogen through the powder. The aluminium oxide was allowed to cool down to approximately 200 °C and a small amount of the methylbenzo[s]picene derivate was added under nitrogen. The mixture was allowed to react for 60-150 min under nitrogen atmosphere. The temperature was varied between 215 and 230 °C. Table 1 shows the different routes used to synthesise the methylindacenopicene (9).

illustration not visible in this excerpt

Table 1 Reaction routes (a) – (g) for the CRC reactions for compound (9)


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Synthesis of Methylated Bucky Bowls by HF elimination
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Bucky Bowls, HF elimination, Molecular switches
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B. Sc. Manuel Langer (Autor:in), 2015, Synthesis of Methylated Bucky Bowls by HF elimination, München, GRIN Verlag,


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