Acetylferrocene

This experiment examines the effect of reaction time, temperature, and mole ratio of reactants on the synthetic yield of acetylferrocene by a Eriedel-Crafts acylation of ferrocene. A central composite experimental design is used to find the optimum conditions, but the experiment could be modified to use a factorial design. 

Friedel-Crafts acylation involves electrophilic attack by acyl cation (CHsCO ) on the ring, and the ring s electronic character should indicate its susceptibility to attack. Compare electrostatic potential maps of ferrocene and acetylferrocene. Which molecule contains the most electron-rich ring Which acylation reaction should be faster Does an acetyl substituent enhance or diminish ring reactivity What should be the major product when ferrocene is combined with one equivalent of acetic anhydride ... 

Nesmeyanov et a/.545 used a mixture of ferrocene, deuterated trifluoroacetic acid and benzene in the molar ratios 1 2 20 in a preliminary investigation of the reactivity of ferrocene and its derivatives. At 25 °C, rate coefficients were 1,620 x 10-7 (ferrocene) and 19.3 xlO-7 (acetylferrocene). In a subsequent publication by Alikhanov and Shatenshtein543 these values were altered to 1,600 x 10-7 and 1.5 x 10 7, respectively, and a value of 0.77 x 10"7 added for 1,1-diacetylferrocene. Under the same conditions, toluene gave a value of 0.3 x 10-7 so that the activating effects of these compounds relative to benzene can be approximately determined. 

Hydrazones are also useful substrates in the preparation of pyrazoles. Reaction of N-monosubstituted hydrazones with nitroolefins led to a regioselective synthesis of substituted pyrazoles <060L3505>. lf/-3-Ferrocenyl-l-phenylpyrazole-4-carboxaldehyde was achieved by condensation of acetylferrocene with phenylhydrazine followed by intramolecular cyclization of the hydrazone obtained under Vilsmeier-Haack conditions <06SL2581>. A one-pot synthesis of oxime derivatives of l-phenyl-3-arylpyrazole-4-carboxaldehydes has been accomplished by the Vilsmeier-Haack reaction of acetophenone phenylhydrazones <06SC3479>. 

The selected electrodes (five n-type and four p-type) were used to obtain kinetic current vs. potential data in solutions containing poised ferrocene redox couples (50% oxidized, 50% reduced) (37.391. The electrode potential was varied over a range of at least 0.5 V to over 1.0 V. Three couples were examined ferrocene (FER) itself, decamethylferrocene (DFER) and acetylferrocene (AFER). The reduction potentials of DFER and AFER with respect to FER (which is assigned a value of 0.0) are -0.50 and +0.25 V, respectively. The reduction potentials for all three couples are located between the CBE and VBE of the WSe2-CH3CN interface. 

Figure 2. Band edge positions obtained over a period of three weeks for p-and n-type WSe2 -CH3CN interfaces containing metallocene redox couples (ferrocene, FER decamethylferrocene, DFER and acetylferrocene, AFER) each at three concentrations (preceding letter refers to high.H medium,M and low, L). Two different electrodes were used to obtain the data for n-WSe2 with doping densities between 1016 -1017 cm-3.

Also, conjugation of a delocalizing ferrocene group with the carbonyl should cause the intense n— -rr carbon-oxygen transition to move to longer wavelengths and bury the feeble CO , . band hence, no such band is identifiable in acetylferrocene and the 267 m maximum most likely correlates with acetophenone s 239 mjx band. 

The exceedingly high reactivity of ferrocene to Friedel-Crafts acylation is exemplified by the fact that mild catalysts such as stannic chloride (63), boron trifluoride (32), zinc chloride (86), and phosphoric acid (29), can be used with considerable success. When ferrocene and anisole were allowed to compete for limited amounts of acetyl chloride and aluminum chloride, acetylferrocene was the sole product isolated, again illustrating the high reactivity of ferrocene toward electrophilic reagents (6). 

Acylmetallocenes undergo many reactions shown by acylbenzenes (35, 87, 91, 116, 124), but a detailed discussion is not presented here. Reductions with either lithium aluminum hydride or sodium borohydride give the corresponding carbinols, while Clemmensen reduction, reduction with lithium aluminum hydride plus aluminum chloride, catalytic hydrogenation, etc., yield corresponding alkyl derivatives. Acetylferrocenes undergo a variety of base condensation reactions and can be oxidized to ferrocenecarboxylic acids without apparent oxidation of the iron atom. 

Arnett and Bushick (2) have determined the pKA values for the conjugate acids of ferrocenyl ketones in aqueous sulfuric acid. They have found, for example, that acetylferrocene is over 2000 times more basic than acetophenone and 85 times more basic than p-hydroxyacetophenone. These data support the concept that metallocenyl groups are strongly electron-releasing compared to the phenyl group and that they possess extraordinary ability to delocalize adjacent positive charges. 

Figure 1. Left Elution of (a) ferrocene and (b) acetylferrocene using APMS as the stationary phase Run conditions 5 1 hexanesethyl acetate, column pressure 7 bar Right Attempted separation of the same molecules using dense 20 pm spheres as the stationary phase. Run conditions 5 1 hexanes ethyl acetate, column pressure 170 bar.

The APMS used for this separation had an average particle size of 4-10 pm Normal phase HPLC of ferrocene and acetylferrocene performed with non-porous 1-3 pm spheres prepared in basic solution showed only one broad peak with no separation of the target molecules. Similarly, 20 pm spheres prepared in acidic solution showed no resolution of the ferrocenes (Figure 1). This indicates that particle size has some effect on the quality of the HPLC separation, but surface area is the major factor provided that the molecules to be separated can access the interiors of the mesoporous particles, which is dependent upon the pore size. (Experiments performed on APMS using confocal scanning laser microscopy indicated that these particles are porous throughout their interiors). 

Light is switched off at +0.5 V vs. SCE for the cathodic sweep. In (a) there is no added reductant (b), (c), and (d) contain 0.5mM ferrocene, 1, l -dimethylferrocene, and acetyl-ferrocene, respectively. Acetylferrocene does not attenuate the surface ferricenium surface ferrocene wave since it is not a sufficiently powerful reductant. Ferrocene and 1, l -dimelhylferrocene both attenuate the surface ferricenium - surface ferrocene wave. But l,l -dimethylferrocene is more effective under identical conditions despite the fact that the same, mass transport-limited, steady-state photocurrent is found for these two reductants. These data suggest that after the light is switched off the reduction of surface ferricenium is controlled partially by mass transport and partly by the electron transfer rate (see text). 

The acetylferrocene does not consume the (FeCp2+)surf., Figure Ad, because the reaction is not thermodynamically spontaneous. The conflict in our data is that steady-state photocurrents for the fast reductants is the same, but the (FeCp2+)surf. can be consumed at different rates in the dark for the various fast reductants. 

The editors are indebted to Dr R. Thomas, Thames Polytechnic, for these experimental details this experiment, and the preparation of acetylferrocene (Expt 6.122), are very suitable as undergraduate exercises. 

A corresponding aldehyde [1.1 mmol, piperonal (a), ferrocene carboxaldehyde (b)] and ketone [1.0 mmol, acetylferrocene (a), 2-methylcyclohexanone (b)] were stirred in an Ehrlenmeyer flask, 2 mmol of powdered KOH added, and the mixture stirred after addition of one drop of Aliquat 336 [see (3.279) and (3.280)]. The Ehrlenmeyer flask was irradiated with microwaves [(a) 3 min, MOW (b) 2 min, MOW] and the final product dissolved in dichloromethane. After filtration on Celite, the solvent was removed and the residue chromatographed on a preparative chromatographic layer of silica (AcOEt/cyclohexane 20/80). The condensation product was further purified by crystallization in ether. Yield (a) 73% (lit. 37%), red solid (b) 63%, red solid. 

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