Back in July, a friend of mine (Tom, who runs the Explosions&Fire YouTube channel) came to Germany in order to record some footage for one of his videos. We managed to schedule a meetup, and naturally we wanted to do some chemistry during that time. I had recently acquired a large amount of 4-benzyl pyridine as part of a bundle, but as it turns out, this chemical is resonably useless apart from replacing pyridine as a base for no particular reason. It has however come to my attention that seemingly noone ever attempted to use it in a Ziegler-Hafner synthesis, and in general the supposed product of this reaction, 6-benzyl azulene, has only been tangentially mentioned in the literature. Therefore, we decided to just go for it. Because the original Zigler-Hafner synthesis is rather annoying since it requires 1-chloro-2,4-dinitrobenzene as a reagent, we instead opted for an alternative method using the corresponding n-butylpyridinium chloride salt.
| Substance | M [g/mol] | n [mmol] | m [g] | V [ml] | Eq. |
|---|---|---|---|---|---|
| 4-Benzyl pyridine | 169.22 | 6.26 | – | 1.00 | 1.0* |
| 1-Chlorobutane | 92.57 | 9.40 | – | 0.99 | 1.5* |
| Dicyclopentadiene | 132.20 | – | – | 7.0 | xs |
| Iron filings | 55.85 | – | 0.020 | – | cat. |
| N,N-Dimethylformamide | 73.09 | – | – | 6.0 | – |
| Sodium hydride (60% in paraffin) | 24.00 | 3.82 | 0.153 | – | 1.0** |
Experimental:
A) 4-Benzyl-N-butylpyridinium chloride
To a 10 ml PTFE lined stainless steel pressure vessel (rated for 3.0 MPa @ 230 °C), 4-benzyl pyridine (1.00 ml, 6.26 mmol, 1.0 eq.) and 1-chlorobutane (0.99 ml, 9.40 mmol, 1.5 eq.) were added. The vessel was sealed, and heated to 130 °C overnight. After cooling to room temperature, the resulting yellow solid was washed twice with hexanes (20 ml) and recrystallized from acetone. 4-Benzyl-N-butylpyridinium chloride was obtained as an off-white, hydroscopic solid (1.07 g, 4.09 mmol, 65%).
B) Sodium cyclopentadienide
All glassware used in this step was previously oven dried. To a 50 ml round bottom flask was added technical grade dicyclopentadiene (7.0 ml), and the solid was heated by means of a silicone oil bath until it was molten (ca. 40 °C). Coarse iron filings (20 mg) were added, and a fractional distillation setup with Raschig column and jacketed dimroth condenser was set up. The apparatus was purged with argon, and the receiving flask was submerged in an ethylene glycol cold bath (-20 °C). The reaction mixture was heated to 175 °C, at which point the mixture started refluxing gently. Cyclopentadiene was gradually distilled over for 5 hours, after which the residue in the distilling flask was allowed to cool to room temperature. The distilled cyclopentadiene was stored at -20 °C over night and used the next day without further purification.
C) 6-Benzyl azulene
All glassware used in this step was previously oven dried. A 10 ml schlenk tube was purged with Argon, and DMF (6.0 ml) as well as sodium hydride (60% suspension in paraffin, 0.153 g, 3.82 mmol, 1.0 eq.) were added at room temperature. The schlenk tube was covered with a silicone septum, and after cooling to 0 °C cyclopentadiene (1.25 ml, 15.28 mmol, 4.0 eq.) was added dropwise to the stirred suspension. A color change from white to light pink occurred while the mixture was stirred for 10 minutes. After warming the suspension to room temperature, 4-Benzyl-N-butylpyridinium chloride was added in one portion, causing the mixture to turn dark red. After stirring for one hour, the septum was replaced with an Argon purged reflux condenser, and the schlenk tube was heated to 160 °C for 6 hours, resulting in a dark green solution. After cooling to room temperature, the crude reaction mix was extracted four times with hexanes (20 ml each, top phase was collected), and the combined extract was filtered thorugh a cotton plug. The bulk of the solvent was removed in vacuo, and the resulting black resin was purified by column chromatography (15 g silica gel type H, Merck, DCM:petrol ether 1:9) to give a blue crystalline solid. Residual cyclopentadiene woudl make further purification necessary to determine a meaningful yield.
Adapted from: A. Székely, Á. Péter, K. Aradi, G. L. Tolnai, Z. Novák, Org. Lett. 2017, 19, 4, 954–957
