Iron(III) Chloride-Silica Gel1

FeCl3-SiO2
(FeCl3)

[7705-08-0]  · Cl3Fe  · Iron(III) Chloride-Silica Gel  · (MW 162.20) (SiO2)

[112926-00-8]  · O2Si  · Iron(III) Chloride-Silica Gel  · (MW 60.09)

(Lewis acid; dehydration;2 acetal cleavage;3,4 rearrangements;2,6,7 thioacetalization;9 mild oxidant; oxidative cyclizations10-13)

Alternate Name: ferric chloride-silica gel.

Form Supplied in: pale yellow powder, 5% wt on silica gel; commercially available.

Preparative Methods: several procedures have been reported for preparation of this reagent depending on the synthetic transformation required. The two procedures described below have been used for cleavage of acetals.1,2

Silica gel (10 g, 70-230 mesh) is added to a solution of FeCl3.6H2O (1.2 g) in acetone at rt. The solvent is removed on a rotary evaporator and the mixture then heated in vacuo at 60 °C for 30 min/0.1 mmHg to yield a yellow powder.1

Anhydrous FeCl3 (4 g) and chromatography grade silica gel (50 g 70-230 mesh) are stirred together in the absence of solvent at rt for 24 h to achieve homogeneous adsorption. A pale yellowish green powder is obtained.2

Handling, Storage, and Precautions: the material obtained by procedure 1 is moisture- and light-sensitive, but can be stored for extended periods under dry nitrogen at rt in a brown bottle. The material obtained in procedure 2 is used immediately. FeCl3 is hygroscopic and corrosive; inhalation or ingestion may be fatal. Silica gel is an irritant. Use in a fume hood.

Lewis Acid.

Iron(III) chloride-silica gel will dehydrate alcohols,1 cleave acetals, open epoxides, rearrange carbonium or oxonium intermediates, catalyze ene reactions, and effect thioacetalization.

Alcohol Dehydration.

FeCl3-SiO2 is an effective reagent for the dehydration of allylic, tertiary, and sterically strained alcohols (eqs 1 and 2). The reaction is carried out by mixing the alcohol with 100× its weight of FeCl3-SiO2 in a volatile solvent, followed by evaporation under a high vacuum; this is usually sufficient to complete the reaction.1 Dehydration of tertiary alcohols has been reported with the reagent prepared by procedure 2.2

Cleavage of Acetals.

The FeCl3-SiO2 reagent cleaves acetals in 2-8 h in chloroform at rt, and is now a well established procedure. Cleavage of TBDMS and trityl ethers is sluggish with typically 30% deprotection after 20 h, which provides for a very mild method for selective deprotections (eq 3). Interestingly, a TBDMS ether can be cleaved without affecting an isopropylidene group in acetone, as the solvent maintains the equilibrium in favor of the isopropylidene group (eq 4).3,4 Benzyl ether cleavage was not observed in the presence of an acetal; chelation of iron to the latter ensures selectivity.3 However, rapid benzyl ether deprotection has been reported in the absence of solvent, essentially using the same procedure as for dehydration.5

Rearrangements.

Tertiary cyclobutanols are converted to cyclopentene derivatives with FeCl3-SiO2 prepared by procedure 2 (eq 5).2,6 Acyloin (eq 6) and pinacol rearrangements1 (eq 7) are also observed with FeCl3-SiO2 from procedure 1. FeCl3-SiO2 has been reported to catalyze intramolecular ene reactions, although Iron(III) Chloride-Alumina is superior.7

Epoxides.

FeCl3-SiO2 containing 2% water facilitates the conversion of epoxides to diols in good yield (eq 8). Anhydrous FeCl3-SiO2 converts epoxides to mixtures of chlorohydrins.1

Thioacetalization.

Carbonyl compounds are thiacetalized with FeCl3-SiO2 (procedure 2) in excellent yields at rt.8 Reaction occurs very rapidly in dichloromethane with 1,2-ethanedithiol, with the color turning from gray to pale yellow indicating completion of the reaction (eq 9); this method works well for hindered and aromatic ketones, unlike many of the alternate procedures.9

Oxidations with FeCl3-SiO2.10

Simple di- and trimethoxybenzenes can be coupled in good yield in dichloromethane with 1.1 equiv of FeCl3-SiO2. Solvent is removed on a rotary evaporator and the mixture is left spinning for 1 h at 30 °C (eq 10).5,11 Precocene II has been dimerized in light petroleum with FeCl3-SiO2 to a mixture of two products (eq 11).12 Intramolecular couplings are observed with appropriately substituted 1,2-diphenylethanes and [2.2]metacyclophanes.5 Tricarbonylcyclohexadieneiron complexes are oxidatively cyclized with FeCl3-SiO2 (eq 12) via concentration from THF on a rotary evaporator (40 min).13 This reaction highlights the moderation in reactivity of this supported reagent as ethanolic FeCl3 can be used to oxidatively disengage an Fe(CO)3-complex ligand.14


1. Keinan, E.; Mazur, Y. JOC 1978, 43, 1022.
2. Fadel, A.; Salaun, J. T 1985, 41, 413.
3. Kim, K. S.; Song, Y. H.; Lee, B. H.; Hahn, C. S. JOC 1986, 51, 404.
4. Fadel, A.; Yefsah, R.; Salaun, J. S 1987, 37.
5. Jempty, T. C.; Gogins, K. A. Z.; Mazur, Y.; Miller, L. L. JOC 1981, 46, 4545.
6. Fadel, A.; Salaun, J. T 1985, 41, 1267.
7. Tietze, L. F.; Beifuss, U. S 1988, 359.
8. Patney, H. K. TL 1991, 32, 2259.
9. Green, T. W. Protective Groups in Organic Synthesis; Wiley: New York, 1981.
10. Bringmann, G.; Walter, R.; Weirich, R. AG(E) 1990, 29, 977.
11. Jempty, T. C.; Miller, L. L.; Mazur, Y. JOC 1980, 45, 749.
12. Fraga, B. M.; Garcia, V. P.; Gonzalez, A. G.; Hernandez, M. G.; Hanson, J. R.; Hitchcock, P. B. JCS(P1) 1983, 2687.
13. (a) Ong, C. W.; Pearson, A. J. TL 1980, 21, 2349. (b) Pearson, A. J.; Ong, C. W. JCS(P1) 1981, 1614.
14. Shvo, Y.; Hazum, E. CC 1974, 336.

Andrew D. White

Parke-Davis Pharmaceutical Research, Ann Arbor, MI, USA



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