Iron(III) Chloride1

FeCl3

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

(mild oxidant capable of phenolic coupling,1 dimerizing aryllithiums6 and ketone enolates;7,8 mild Lewis acid: catalyzes ene reactions,21 Nazarov cyclizations,18-20 Michael additions,24 and acetonations29)

Alternate Name: ferric chloride.

Physical Data: mp 306 °C; d 2.898 g cm-3.25

Solubility: 74.4 g/100 mL cold water, 535.7 g mL-1 boiling water; v sol alcohol, MeOH, ether, 63 g mL-1 in acetone (18 °C).

Form Supplied in: black crystalline powder; widely available.

Preparative Methods: anhydrous FeCl3 available commercially is adequate for most purposes. However, the anhydrous material can be obtained from the hydrate by drying with thionyl chloride7 or azeotropic distillation with benzene.12

Handling, Storage, and Precautions: is hygroscopic and corrosive; inhalation or ingestion may be fatal. It causes eye and skin irritation. It should be stored and handled under an inert dry atmosphere.36 Use in a fume hood.

Oxidative Properties.1

FeCl3 oxidizes a wide array of functionalities, such as certain phenols to quinones (eq 1), dithiols to disulfides (eq 2), and 2-hydroxycyclohexanone to 1,2-cyclohexanedione.1 Inter- and intramolecular oxidative dimerization of aromatics gives rise to such products as magnolol, metacyclophanes,1 and crinine alkaloids (eq 3).2 Phenolic ethylamines and N-acetyloxyamides can be cyclized to indoles (eq 4)3 and oxindoles (eq 5),4 respectively. Dimerization of aryllithium or Grignard reagents yields intermediates for cyclophane5 and perylenequinone6 synthesis (eq 6). Inter-7 and intramolecular8 ketone enolates can be converted to 1,4-diketones (eq 7), and lithium salts of allylic sulfones afford 1,6-disulfones.9

Stereoselective cross-coupling of alkenyl halides with Grignard reagents is catalyzed by FeCl3 (45-83%) (eqs 8 and 9).10 Propargyl halides also react to afford allenes.11 A study of FeIII catalysts revealed that Tris(dibenzoylmethide)iron(III) was the most useful.12

Alkylcyclopentanones can be dehydrogenated to cyclopentenones, but Copper(I) Chloride is a better catalyst.13 Trimethylsilyloxybicyclo[n.1.0]alkanes can be oxidatively cleaved, providing a three-step method of ring expansion (eq 10).14 Cycloalkanones are cleaved with FeCl3/MeOH under O2 to o-oxo esters; this reaction works best with flanking methyl groups (eq 11).15 Photooxidation of alkenes with FeCl3 can yield a variety of useful chloroketones depending on the starting material,16 and photoreaction of carbohydrates in pyridine induces a selective C(1)-C(2) bond cleavage, in contrast to Titanium(IV) Chloride (C(5)-C(6) cleavage) (eq 12).17 FeCl3/EtOH can also be used to disengage tricarbonyliron complex ligands.

Lewis Acid Mediated Reactions.

Silicon-directed Nazarov cyclizations occur readily in dichloromethane catalyzed by FeCl3, utilizing the cation-stabilizing effect of silicon.18 Cyclohexenyl systems afford only cis-fused ring products. The reaction has been elaborated to the preparation of linear tricycles with b-silyldivinyl ketones at low temperature (eq 13).19 Optically active b-silyl divinyl ketones have been used to demonstrate that cyclization occurs with essentially complete control by silicon in the anti SE sense.20 FeCl3 is the best Lewis acid catalyst for the intramolecular ene reaction of the Knoevenagel adduct from citronellal and dimethyl malonate at low temperature (eq 14).21 However, the basic alumina supported catalyst can give more reliable results. The ene reaction of an unsaturated ester of an allylic alcohol yields a chlorolactone cleanly at 25 °C.22 This reaction produces only one of four possible diastereomers, with clean trans addition to the double bond occurring (eq 15). 1-Silyloxycycloalkanecarbaldehydes undergo ring expansion to 2-silyloxycycloalkanones (82-89%) (eq 16). FeCl3 catalysis provides the best selectivity derived from rearrangement of the more substituted a-carbon atom.23 FeCl3-catalyzed addition of primary and secondary amines to acrylates occurs exclusively 1,4 with no polymerization (79-97%) (eq 17).24

In the field of protecting group chemistry FeCl3 will cleave benzyl25 and silyl ethers,26 convert MEM ethers to carboxylic esters,27 and when dispersed on 3Å molecular sieves catalyzes the formation of MOM ethers.28 In the area of carbohydrate chemistry, FeCl3 is proving a versatile reagent for acetylation, acetonation, acetolysis, transesterification, O-glycosidation of b-per-O-acetates, formation of oxazolines, direct conversion of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-acylamido-b-D-glucopyranoses into their O-glycosides, preparation of 1-thioalkyl(aryl)-b-D-hexopyranosides from the peracetylated hexopyranoses having a 1,2-trans configuration,29 and as an anomerization catalyst for the preparation of alkyl-a-glycopyranosides (eq 18).30

Substituted amidines have been prepared from a nitrile compound, an alkyl halide, an amine, and FeCl3 in a one-pot synthesis (40-80%) (eq 19).31 FeCl3 in ether converts epoxides into chlorohydrins. Fused bicyclic epoxides yield trans-chlorohydrins (eq 20).32 Friedel-Crafts acylation of activated (Me, OMe substituents) aromatics occurs readily with optically active N-phthaloyl-a-amino acid chlorides catalyzed by FeCl3 (1-5 mol%).33 Trialkylboranes react with FeCl3 in THF/H2O to afford alkyl chlorides in excellent yield.34 t-Alkyl and benzylic chlorides can be converted to the iodides on reaction with Sodium Iodide in benzene catalyzed by FeCl3.35

Related Reagents.

Iron(III) Chloride-Acetic Anhydride; Iron(III) Chloride-Alumina; Iron(III) Chloride-Dimethylformamide; Iron(III) Chloride-Silica Gel; Iron(III) Chloride-Sodium Hydride.


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15. Ito, S.; Matsumoto, M. JOC 1983, 48, 1133.
16. Kohda, A.; Nagayoshi, K.; Maemoto, K.; Sato, T. JOC 1983, 48, 425.
17. Ichikawa, S.; Tomita, I.; Hosaka, A.; Sato, T. BCJ 1988, 61, 513.
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20. Denmark, S. E.; Wallace, M. A.; Walker, C. B., Jr. JOC 1990, 55, 5543.
21. Tietze, L. F.; Beifuss, U. S 1988, 359.
22. Snider, B. B.; Roush, D. M. JOC 1979, 44, 4229.
23. Matsuda, T.; Tanino, K.; Kuwajima, I. TL 1989, 30, 4267.
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28. Patney, H. K. SL 1992, 567.
29. Dasgupta, F.; Garegg, P. J. ACS 1989, 43, 471 and references therein.
30. Ikemoto, N.; Kim, O. K.; Lo, L.-C.; Satyanarayana, V.; Chang, M.; Nakanishi, K. TL 1992, 33, 4295.
31. Fuks, R. T 1973, 29, 2147.
32. Kagan, J.; Firth, B. E.; Shih, N. Y.; Boyajian, C. G. JOC 1977, 42, 343.
33. Effenberger, F.; Steegmuller, D. CB 1988, 121, 117 (CA 1988, 108, 75 799z).
34. Arase, A.; Masuda, Y.; Suzuki, A. BCJ 1974, 47, 2511.
35. Miller, J. A.; Nunn, M. J. JCS(P1) 1976, 416.
36. Sigma-Aldrich Library of Chemical Safety Data, 2nd ed.; Lenga, R. E., Ed.; Sigma-Aldrich: Milwaukee, WI, 1988; p 1680A.

Andrew D. White

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



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