[18]Annulene (CAS NO.: ), which is also known as 1,3,5,7,9,11,13,15,17-Cyclooctadecanonaene, could be produced through the following synthetic routes.

A. Hexadehydro[18]annulene. A 12-l., four-necked, round-bottomed flask provided with a stopcock at the bottom (Figure 1) is fitted with a stirrer, a reflux condenser, and a 500-ml. pressure-equalizing dropping funnel. The flask is placed in a large metal vessel equipped with a hot–cold water inlet and a drain. The flask is charged with 600 g. (3.00 moles) of copper(II) acetate monohydrate and 3.8 l. of pyridine. Stirring is begun and warm water is added to the metal vessel to heat the contents of the flask to 55 ± 1°, and the mixture is slowly stirred at this temperature for 1 hour. With vigorous stirring (approximately 600 r.p.m.), a solution of 50 g. (0.64 mole) of 1,5-hexadiyne in 400 ml. of pyridine is added over 30 minutes to the 55°, green suspension. The mixture is stirred vigorously at this temperature for an additional 2 hours before the warm water in the metal vessel is allowed to drain and is replaced with a mixture of ice and water. When the contents of the flask have cooled, the mixture is drawn off through the stopcock at the bottom of the flask and filtered through a 25-cm. Büchner funnel (Filtrate A). The green residue is transferred to a 5-l. beaker and 2.5 l. of 1:1 (v/v) benzene–diethyl ether is added. The mixture is stirred well, avoiding emulsion formation, and filtered (Filtrate B). The residue is similarly extracted with 2.5 l. of 1:1 (v/v) benzene–ether and filtered (Filtrate C). Each filtrate is kept separate.

                                                            Figure 1.

Filtrate A is concentrated to approximately 200 ml. and added to Filtrate C. The resulting mixture is well agitated and filtered through a 25-cm. Büchner funnel. The residue is extracted twice in a similar manner with 500 ml. of 1:1 (v/v) benzene–ether. All the filtrates are now combined in the original 12-l. reaction vessel and washed successively with two 500-ml. portions of water, two 500-ml. portions of cold (0°), 2 N hydrochloric acid, and three 500 ml portions of water. The organic layer is dried for 2 hours over ca. 110 g. of magnesium sulfate, filtered, and evaporated to dryness, yielding approximately 16 g. of crude product.

B. Tridehydro[18]annulene. The dark brown residue from Part A and 800 ml. of benzene are added to a 2-l., round-bottomed flask fitted with a reflux condenser and a calcium chloride drying tube. The solid dissolves on heating to reflux, then the solution is allowed to cool briefly. The condenser is removed, and 800 ml. of a saturated solution of potassium tert-butoxide in tert-butyl alcohol is rapidly added. After the resulting solution is heated to reflux for 30 minutes, the hot mixture is transferred to the original 12-l. reaction vessel, which contains approximately 2 l. of ice, and 1.5 l. of ether is added. The resulting mixture is stirred well then allowed to stand for a few minutes. The incompletely separated phases, in which is suspended a large amount of black solid, are filtered through a 25-cm. Büchner funnel. Whenever the filtration becomes slow, the black material on the filter paper is washed with ether, and the paper is replaced. The organic layer of the filtrate is separated, washed three times with 500-ml. portions of water, dried for 2 hours over ca. 100 g. of anhydrous magnesium sulfate, filtered, and evaporated to dryness. The red-brown viscous residue is dissolved in 60 ml. of benzene and chromatographed on alumina.

One liter of 95:5 (v/v) pentane–ether is poured into a closed chromatography column (100 × 4.5 cm.), the bottom of which is protected by a small plug of cotton wool. One kilogram of alumina is added in portions, with slow rotation by hand. The stopcock is opened, and the level of the supernatant liquid is allowed to fall to the top of the alumina. The benzene solution is now added with a long pipette and is allowed to seep in. The column is developed first with 1 l. of 95:5 (v/v) pentane–ether in order to wash out the benzene, then with 80:20 (v/v) pentane–ether. Two bands are observable on the column. The faster moving, light brown band consists of tridehydro[18]annulene and the slower moving, dark brown band consists of tetradehydro[24]annulene. When the first band is approximately 15 cm. from the bottom of the column, after approximately 4–6 l. of solvent have been eluted, 150-ml. fractions are collected, and the electronic spectrum of each fraction is determined. As soon as the maxima at 385 and 400 mm. characteristic of tridehydro[18]annulene appear, the fractions are combined ("mixed fractions") until the first band is approximately 1 cm. from the bottom of the column. Essentially "pure" tridehydro[18]annulene is now eluted, and this material is collected until the second band is approximately 5 cm. from the bottom of the column. Smaller fractions (150 ml. each) are now collected again; the electronic spectrum of each fraction is determined, and those still showing maxima at 385 and 400 nm. are combined with the previously mentioned "mixed fractions." If required, the tetradehydro[24]annulene suitable for conversion to [24]annulene can then be eluted with pentane–ether (70:30 to 50:50).

The electronic spectrum of the fractions containing the "pure" tridehydro[18]annulene exhibits the strongest absorption maximum (in benzene) at 342 nm. (ε 155,000) and the spectroscopic yield, based on the molar extinction coefficient, is 1.17 g. (2.40% from 1,5-hexadiyne). The yield of tridehydro[18]annulene in the "mixed fractions," based on the 342 nm. maximum, is 0.27 g. (0.55%). The tridehydro[18]annulene is best stored in solution in the refrigerator.

C. [18]Annulene. In a 300-ml., conical flask fitted with a side arm (with a closed stopcock) and a 3.5-cm. ®-coated magnetic stirring bar is placed 1 g. of a 10% palladium-on-calcium carbonate catalyst and 30 ml. of benzene. The flask is attached to an atmospheric pressure hydrogenation apparatus, and the air in the system is replaced by hydrogen by evacuating the flask and refilling with hydrogen three times. The catalyst suspension is stirred until no more gas is absorbed. One-third (390 mg., determined spectroscopically) of the "pure" tridehydro[18]annulene solution described in Part B is evaporated to dryness, and the resulting brown crystalline residue is dissolved in 30 ml. of benzene. This solution is added to the hydrogenation flask through the side arm without stirring. The mixture is now stirred under a hydrogen atmosphere as rapidly as possible (ca. 600 r.p.m.) until 207 ml. (4.9 molar equivalents) of gas (22°, 740 mm.) are absorbed over ca. 5 minutes. The mixture is filtered through a sintered glass funnel, and the catalyst is washed with three 20-ml. portions of benzene.

This hydrogenation experiment is repeated twice with the remaining two-thirds of the "pure" tridehydro[18]annulene solution, and the combined filtrates from the three hydrogenations are evaporated to approximately 30 ml. The solution is then transferred with a pipette to a test tube (10 × 3 cm.) and concentrated to approximately 15 ml. at 40° with a stream of nitrogen. The dark green solution is diluted with 20 ml. of ether and cooled in an ice bath for 30 minutes. The resulting red-brown crystals of [18]annulene are collected by filtration on a sintered glass funnel and washed with approximately 3 ml. of cold (-20°) ether. After drying in air for a few minutes this material weighs 114 mg. A second crop weighing 42 mg. is obtained by evaporation of the mother liquors to dryness, followed by crystallization from 6 ml. of benzene and 20 ml. of ether. Both crops give a single spot on TLC.

The [18]annulene mother liquors contain 181 mg. of unchanged tridehydro[18]annulene, as determined by the electronic spectrum (see Part B). They are combined with the "mixed fractions" described in Part B (containing 270 mg. of tridehydro[18]annulene), and the resulting solution is evaporated to dryness. The residue is dissolved in 30 ml. of benzene and stirred with hydrogen and 1.0 g. of a 10% palladium-on-calcium carbonate catalyst, as before, until 216 ml. (4.4 molar equivalents) of hydrogen (20°, 740 mm.) are absorbed. The catalyst is removed, and the filtrate is concentrated to approximately 6 ml., as described previously. After the addition of 20 ml. of ether and cooling in an ice bath, 112 mg. of [18]annulene is collected by filtration. The purity of the product is confirmed by TLC. The total yield of [18]annulene is 268 mg. (0.54% overall from 1,5-hexadiyne.

[18]Annulene is best stored in benzene–ether solution in the refrigerator. The crystals can also be kept for some time in the refrigerator, small crystals being less stable than large ones. Material that has decomposed to some extent may be purified as follows. The substance (300 mg.) is broken up with a spatula and heated with 30 ml. of benzene, and the insoluble material is removed by filtration. The filtrate is poured onto a chromatography column (20 × 1.8 cm.), prepared with 35 g. of alumina and benzene. The column is washed with benzene until the eluate is colorless. Polymeric material is retained at the top of the column. The eluent is concentrated to approximately 6 ml., diluted with 20 ml. of ether, and cooled in an ice–salt bath. The resulting crystals of [18]annulene are collected on a sintered glass funnel, washed with 3 ml. of cold (-20°) ether, and dried in air for a few minutes.