Ferrocenecarboxylic acid chloride

Ferrocene,136 ferrocenecarboxaldehyde,137 and hydroxymethyl-and hydroxyethylferrocene138 have all been used to prepare various ferrocenylcarbohydrates. Ferrocenecarboxylic acid chloride and 1,3-O-methyleneglycerol139, 140 gave the ferrocenecarboxylate (163). 

The ligand, 1 -[4-(5)-terf-butyl-2-oxazolin-2-yl]-2-(.S )-(diphenylphosphino)fcrro-cene (1), is prepared in three steps from readily available ferrocenecarboxylic acid chloride (5).[4] The steps involved are firstly amide bond formation secondly cyclisation to the oxazoline and finally diastereoselective lithiation/phosphinylation to afford (1) (Figure 5.4). 

Ferrocenecarboxylic acid chloride (1.10 g, 4.4 mmol) was placed in a 100-mL round-bottomed flask equipped with a magnetic stirrer bar, under a nitrogen atmosphere. Dry dichloromethane (25 mL) was added and the resulting solution was stirred at 25 °C. A solution of (S)-terf-leucinol (0.51 g, 4.4 mmol) in dry dichloromethane (25 ml) was added followed by triethylamine (0.61ml, 4.4 mmol) and stirring was continued at 25 °C for 20 hours. 

Aminothiazole reacts with both ferrocenecarboxaldehyde and ferrocenecarboxylic acid chlorideto give the expected imine and amide, respectively. Ferrocenecarboxylic acid chloride also reacts with phenothiazine to give both N- and C-acetylation. Ferrocene-carboxaldehyde and rhodanine gave 134, while reaction of the thiosemicarbazone of ferrocenecarboxaldehyde with chloroacetic acid in acetic acid gave 135. ... 

A useful synthetic technique involves the acylation of ferrocene with di-phenylcarbamyl chloride and aluminum chloride (50). The product, diphenyl-carbamylferrocene (X), is readily hydrolyzed to ferrocenecarboxylic acid (XI). Acylation of X followed by hydrolysis produces good yields of l -acylferrocene-carboxylic acids. 

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. 

Fc-amino acids and Fc-peptides have been prepared by various different methods. Most of them use commercially available ferrocenecarboxylic acid (FcOH, 1) or ferro-cenecarboxylic acid chloride (FcCl, 2). Historically, amide bond formation was achieved starting from 2 and a suitable amino component, such as an amino acid or peptide, having an available NH2 group, to give the desired Fc-amino acid esters (3) or Fc-peptides (4) (Scheme 1). 

Glucose oxidase [E.C. 1.1.3.4.] type X and D-amino-arid-oxidase [E.C. 1.4.3.3.] type I were purchased from Sigma. Na-HEPES (sodium 4-(2-hydroxy-ethyl) -1-piperazinethane sulfonate), DEC [1-(3-dimethylaminopropyl)-3-ethylcarboiimide.HCl], ferrocenecarboxylic acid, isonicotinoyl chloride. HCl and 4-aminopyridine were purchased from Aldrich, and Sephadex G-15 and Sephadex C-25 from Pharmacia Fine Chemicals. [Ru(NH3)5Cl]Cl2 was prepared from [Ru(NH3)6]Cl3 (Johnson Matthey), following a reported procedure . Ferrocylacetic acid was made from N,N-dimethylaminoethylferrocene (Aldrich) by a reported procedure . ... 

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