Abstract

The purpose of this experiment is to perform a microscale synthesis of acetylferrocene from ferrocene and acetic anhydride in an acid-catalyzed (85% H3PO4) Friedel-Crafts reaction. Solutions of pure ferrocene and acetylferrocene, crude isolated product and column purified reaction product will be prepared and analyzed using the Thermo Scientific™ picoSpin™ 45 NMR spectrometer.

Two lesson plans are available

Introduction

The Friedel-Crafts reaction represents a very important and broad class of electrophilic aromatic substitution reactions. The acylation reaction utilizes a Lewis acid catalyst, such as BF3 or AlCl3, to produce an acyl cation that adds to the aromatic ring. Important reagents for acylation are acyl halides, carboxylic acids, anhydrides and ketenes. The alkyl group R in the acylating reagent can be an aryl or alkyl group. Acylation does not suffer from R-group rearrangement to a more stable carbocation species suffered by R groups Friedel-Crafts alkylation reactions, a major disadvantage, because electrophilic attack in acylation is via an acylium ion (an acyl cation, RC≡O+). With anhydrides, the mineral acid phosphoric acid (H3PO4) can be used as the Lewis acid catalyst, and acylation with nitriles (RCN; the Hoesch reaction) employs HCl and ZnCl2.

Acylation requires an electron rich aromatic ring system and cannot contain any electron withdrawing substituents on the ring. Ferrocene (bis(η5-cyclopentadienyl)iron; Fe(C5H4COCH3)2) is an organometallic compound containing iron (Fe) "sandwiched" between two cyclopentadienyl rings opposite the central metal atom. The cyclopentadienyl rings are aromatic according to Hückel rule, they are planar, cyclic, conjugated and satisfy the 4n+2 rule. Because of their high electron density, acylation of ferrocene is accomplished under milder conditions using a phosphoric acid as acid catalyst. The acyl group (RCO) is deactivated, stopping the reaction cleanly after the addition of one group per aromatic ring. Thus, in this microscale Friedel-Crafts acylation reaction of ferrocene with acetic anhydride using a phosphoric acid as the Lewis acid catalyst, the major reaction is acetylferrocene ([Fe(C5H4COCH3)(C5H5)]), with minor presence of diacetylferrocene (Fe(C5H4COCH3)2). The reaction product is isolated and purified by microscale flash column chromatography.

Column chromatography is one of many basic laboratory techniques taught in organic chemistry. It has widespread applications in the organic synthetic lab because of its efficiency for separating and purifying components of a mixture. It can be applied to both liquid and solid samples, and multi-component mixtures. On a small scale, column chromatography is fast and cost effective. It is particularly useful for separating reaction mixtures containing reactants, products and byproducts.

Chromatography takes advantage of the differences in polarity and binding strength that the components of a mixture have for column adsorbents. Adsorbents are high surface area stationary phase materials that bind solute molecules. A mobile phase solvent, or eluent, is used to desorb solute molecules, carrying them along the column to a receiving flask. As the solvent polarity is increased, polar molecules bound more strongly to the column begin to solubilize and are carried down the column in the mobile phase. Equilibrium is established between binding to the stationary phase and solubility in the mobile phase. As the solvent polarity increases, more tightly bound polar molecules, firmly held by the adsorbent, establish equilibrium with the eluting solvent and flow along the column. This process is analogous to thin layer chromatography (TLC), gas chromatography (GC) and high-performance liquid-phase chromatography (HPLC).

About the author

Dean Antic, Ph.D., is a Senior NMR Applications Scientist, organic chemist and spectroscopist at Thermo Fisher Scientific, San Diego, CA. Formerly, Dean was an adjunct professor of chemistry at Northeastern Illinois University and a certified 9-12 chemistry instructor.

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