Organic Synthesis

Acetylation of ferrocene

Theory: 

Acylation of aromatic ring is accomplished by Friedel-Crafts reaction using an acid as a catalyzator. In ferrocene (bis(η5-cyclopentadienyl)iron), two cyklopentadienyl aromatic rings coordinating to a central atom Fe(II) are found. Using mild condition (phosphoric acid and acetic anhydride) yields a monoacetylated product besides unchanged ferrocene (Scheme 1) [1]. The mixture is then separated by elution chromatography.

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Scheme 1 Acetylation of ferrocene by phosphoric acid/acetic anhydride mixture

The most common combination of reagents used for Friedel-Crafts acetylation  is a mixture of anhydrous aluminium(III) chloride and acetyl chloride. The reaction requires anhydrous condition and is done in DCM (dichlormethane). The reaction mixture is protected by CaCl2 drying tube or it is carried out in inert atmosphere of nitrogen gas.  The reaction has a tendency to over-react forming di-substituted product. This can be controlled by changing a molar ratio of the reactants. An inactivation effect on the aromatic ring of the acetyl group leads preferably to a formation of 1,1’-diacetylated product. 1,2-diacetylated ferrocene and 1,3-diacetylated ferrocene are the minor products.

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Picture 1 (a) monoacetylated ferrocene, (b) 1,1′-diacetylated ferrocene, (c) 1,2-diacetylated ferrocene, (d) 1,3-diacetylated ferrocene

The forms are separated by elution chromatography and differentiated by H-NMR spectroscopy. In the reaction, a ferrocenium ion is produced as a side-product. The ion is blue colored and paramagnetic. It is separated from the mixture by washing with water. It can be reversibly reduced to ferrocene by thiosulphate or ascorbic acid. An example of ferrocenium ion preparation is a reaction of ferrocene with iron(III) chloride

Fc + FeCl3 → Fc+Cl + FeCl2

Procedure:

To the 100 mL round bottom flask anhydrous aluminium chloride (0.44 g, 3.3 mmol) was placed followed by addition of 25 mL dichloromethane and ferrocene (0.56 g, 3 mmol) under the constant stirring. Acetyl chloride (0.25 mL, 3.3 mmol) was added slowly from the pipette. A drying tube filled with CaCl2 was attached to the flask and the mixture was stirred vigorously for 30 minutes.  The reaction progress was determined by TLC chromatography. After the reaction was over, additional 10 mL of dichloromethane was added to the mixture followed by 50 mL of water. The mixture was transferred to a separation funnel and the lower organic phase was separated. It was then washed three-times with 10 mL of water, dried over anhydrous sodium sulphate, filtered and the solvent was distilled off using RVE. The solid mixture that crystallized was dissolved in a small amount of cyclohexane/ethyl acetate mixture (2:1) and separated by column chromatography (Picture 2). Yield: 61,8 %.

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Picture 2 (a) 5 min, CH/EAc (6:1), (b) 10 min, CH/EAc (2:1), (c) 30 min, CH/EAc (2:1), (d) monoacetylated product after column chromatography, CH/EAc (2:1)

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Literature:

[1] GRAHAM, P.J., et al. J. Am. Chem. Soc. 1957, Vol. 79, p. 3416.