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RE: ORGLIST problems with Friedel Craft reaction

From: "Ismail, Fyaz" <F.M.Ismail>
Subject: RE: ORGLIST problems with Friedel Craft reaction
Date: Thu, 23 Jun 2011 16:20:54 +0000
Dear Alok,
Aluminium chloride should be freshly sublimed and stored under dry nitrogen and argoin for best results. 

The work you refer to is partly based on that of Robert Burns Woodward et al. In the first short communication, Woodward et al. suggest that using carbon disulphide and aluminium chloride results in the diacetyl derivative [1]. Subsequently, in a detailed full paper Rosenblum and Woodward [2], reveal a preparation for diacetylation which may explain your conundrum. For an early seminal review on ferrocene reactivity see Pauson [3]. 
The (mono-) acetylation of ferrocene is best carried out using conditions in which 85% metaphosphoric acid is used in conjunction with acetic anhydride. However, this procedure does result in the formation of both mono- and di-acetylation due to the enhance reactivity of the mono-actylferrocene (compared to the parent ferrocene) and requires chromatography to provide pure products. The course of the reaction can easily be monitored by TLC. 

For instance, you could use the method suggested by Graham et al. [4] who suggest the folowing. Procedure: A mixture of 93 g. (0.6 mole) of ferrocene, 250 ml. of acetic anhydride and 20 ml. of 85% phosphoric acid was heated at 100° for 10 minutes. The reaction mixture was cooled slightly and poured onto ice. After standing overnight, the mixture was neutralized with aqueous sodium carbonate monohydrate (200 g. dissolved in 200 ml. of distilled water). The resultant brown pasty mass was cooled in an ice-bath and filtered. The tan product was thoroughly washed with distilled water (4 x 100-ml.) and filtered. The product was dried overnight in a vacuum desiccator [P2O5]. Sublimation of the crude product at 100° (1 mm.) gave 81.5 g. (71 % yield) of an orange crystalline product (m.p. 85-86 °C; recrystallization from n-heptane).


A simple procedure (suitable for undergraduate laboratories) has been described in various textbooks and journals. For instance, Herz [5] states that: Ferrocene (4.6 g) was dissolved with magnetic stirring in 125 ml. acetic anhydride. The flask was then cooled (water bath) keeping the internal temperature at 25°C while I0 ml of 85% phosphoric acid was slowly added. Subsequently, the water bath was exchanged for a bath at various temperatures (e.g. 30°, 45° or 60°C) and a 2-5-ml aliquot was removed from the reaction mixture, poured on ice, neutralized with sodium hydrogen carbonate, and the aqueous solution extracted with methylene chloride (or diethylether). After drying and evaporation of the solvent, the ferrocene mixture was dissolved in methylene chloride and subjected to TLC." Herz used benzene/ethanol (30:l, v/v). In this system, ferrocene has a Rf = 0.9, acetyl ferrocene Rf = 0.53, and diacetyl ferrocene Rf = 0.25. Their best experimental conditions were 20°C for 16 hr. Obviously, you should avoid the use of toxic benzene, so hexanes/ethyl acetate (4:1, v/v) is one suitable substitute solvent system.

If you favour the use of (or like us, exclusively use) microwaves then see the work of  Garringer et al. [6]. Procedure: Acetylferrocene. To a 10 mL reaction vial equipped with a magnetic stirrer was charged ferrocene (0.20 g, 0.80 mmol), acetic anhydride (0.74 mL, 8.0 mmol, 10 equiv), and one drop of concentrated phosphoric acid acting as a catalyst. The vial was sealed (septum cap) and allowed to purge under dry nitrogen (10 min) using a double vacuum manifold. The sealed vial was then heated in a CEM focused microwave reactor (300 W, 5 min, 125°C, max T = 134 °C, max; P = 25 psi). The dark red (oily) mass was diluted with methylene chloride (35 mL) and transferred to a separating funnel. It was then washed with distilled water (25 mL), then aqueous NaHCO3 (25 mL), dried over MgSO4, and concentrated in vacuo to give a dark red-orange solid. Chromatography (hexanes/ethyl acetate 4:1, v/v) provided 0.17 g (75%) of the desired acetyl ferrocene; (m.p. 85-86 °C; recrystallization from n-heptane).

References
[1] R.B. Woodward, M. Rosenblum and M. Whiting, A New Aromatic System. J. Am Chem Soc., 1952, 74, 3458.
[2] M. Rosenblum, R. B. Woodward J. Am Chem Soc., 1958, 80 (20), 5443.
[3] P.L. Pauson, Quart Rev (London) 1955, 9, 392. 
[4] P. J. Graham, R. V. Lindsey, G. W. Parshall, M. L. Peterson, G. M. Whitman Some Acyl Ferrocenes and their Reactions. J. Am. Chem. Soc., 1957, 79 (13), 3416.
[5] J. E. Herz. Optimizing experimental conditions: The use of TLC to follow the course of a reaction J. Chem. Educ., 1966, 43 (11), 599.
[6] S. M. Garringer, A. J. Hesse, J. R. Magers, K. R. Pugh, S. A. O'Reilly,  A. M. Wilson. Microwave Synthesis of Benchmark Organo-Iron Complexes. Organometallics 2009 28 (23), 6841.


Dr. Fyaz M. D. Ismail,
Institute for Health Research,
Medicinal Chemistry Research Group,
School of Pharmacy & Biomolecular Sciences
Liverpool John Moores University
Liverpool L3 3AF

-----Original Message-----
From: orglist-everybody [mailto:orglist-everybody] On Behalf Of Alok Shaurya
Sent: 23 June 2011 06:55
To: OrgList
Subject: ORGLIST problems with Friedel Craft reaction

Dear all,

I have been doing Friedel Craft acylation of ferrocene for quite a
while now. At first the reaction went smoothly and gave good yields
(85-90%). But for last three times whenever I try to run the reaction
the solution first turns to purple (as expected), characteristic of
Friedel Craft, but after about 10 min it turns dark green as if the
AlCl3 has been destroyed and the yield comes to as low as 10% (that
too mono and di acylated products combined, I am trying di-acylation
here). I use dry conditions and all but I am not able to figure out
what could be the source of error here. I read somewhere in this forum
that AlCl3 bottle if fumes when opens is fir for FC rxn, I checked
mine and it fumes.
Please comment.

The protocol I use is as follows:
1. Dissolve 2 gm of ferrocene in 10mL dry DCM and 4mL Acetyl Chloride.
Purge it with N2 for a min.
2. Dissolve 4 gm of AlCl3 in 10 mL of dry DCM in a two necked RB flask
equipped with a reflux with a drying tube on top of it.
3. Using a dry syringe, transfer the first solution to RB Flask, while
stirring, dropwise.
4. Reflux overnight at RT while stirring.
5. At first the solution changes to purple (expected) but after about
10 min it turns dark green.

--
Alok Shaurya

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