Cerium(IV) Ammonium Nitrate1


[16774-21-3]  · CeH8N8O18  · Cerium(IV) Ammonium Nitrate  · (MW 548.26)

(volumetric standard oxidant;2 oxidant for many functional groups;1 can promote oxidative halogenation3)

Alternate Name: ammonium cerium(IV) nitrate; ceric ammonium nitrate; CAN.

Solubility: sol water (1.41 g mL-1 at 25 °C, 2.27 g mL-1 at 80 °C); sol nitric acid.

Form Supplied in: orange crystals; widely available.

Handling, Storage, and Precautions: solid used as supplied. No toxicity data available, but cerium is reputed to be of low toxicity.

Functional Group Oxidation.

CeIV in acidic media is a stronger oxidant than elemental chlorine and is exceeded in oxidizing power only by a few reagents (F2, XeO3, Ag2+, O3, HN3). The thermodynamically unstable solutions can be kept for days because of kinetic stability. CAN is a one-electron oxidant soluble in water and to a smaller extent in polar solvents such as acetic acid. Its consumption can be judged by the fading of an orange color to pale yellow, if the substrate or product is not strongly colored. Because of its extremely limited solubility in common organic solvents, oxidations are often carried out in mixed solvents such as aqueous acetonitrile. There are advantages in using dual oxidant systems in which CeIV is present in catalytic amounts. Cooxidants such as Sodium Bromate,4 t-Butyl Hydroperoxide,5 and Oxygen6 have been employed. Electrolytic recycling7 of CeIV species is also possible.

Cerium(IV) sulfate and a few other ligand-modified CAN reagents have been used for the oxidation. The differences in their oxidation patterns are small, and consequently it is quite safe to replace one particular oxidizing system with another. More rarely employed is cerium(IV) perchlorate.

Oxidation of Alkenes and Arenes.

The outcome of the oxidation of alkenes is solvent dependent, but dinitroxylation (eq 1)8 has been achieved. Certain arylcyclopropanes are converted into the 1,3-diol dinitrates.9

CAN promotes benzylic oxidation of arenes,10 e.g. methyl groups are converted into formyl groups but less efficiently when an electron-withdrawing group is present in the aromatic ring. A very interesting molecule, hexaoxo[16]orthocyclophane in an internal acetal form (eq 2),11 has been generated via CAN oxidation. Regioselective oxidation is observed with certain substrates, e.g. 2,4-dimethylanisole gives 3-methyl-p-anisaldehyde. Oxidation may be diverted into formation of non-aldehyde products by using different media: benzylic acetates12 are formed in glacial acetic acid, ethers13 in alcohol solvents, and nitrates14 in acetonitrile under photolytic conditions.

Polynuclear aromatic systems can be oxidized to quinones,15 but unsymmetrical substrates will often give a mixture of products. It has been reported that mononitro derivatives were formed by the oxidation of polynuclear arenes with CAN adsorbed in silica,16 whereas dinitro compounds and quinones were obtained from oxidation in solution.

Oxidation of Alcohols, Phenols, and Ethers.

A primary alcohol can be retained when a secondary alcohol is oxidized to ketone.17 Tetrahydrofuran formation (eq 3)18 predominates in molecules with rigid frameworks, which are favorable to d-hydrogen abstraction by an alkoxyl radical.

Tertiary alcohols are prone to fragmentation;19 this process is facilitated by a b-trimethylsilyl group (eq 4)20. Other alcohols prone to fragmentation are cyclobutanols,21 strained bicyclo[x.y.z]alkan-2-ols,22 and homoallylic alcohols.18d

CAN converts benzylic alcohols into carbonyl compounds.23 Even p-nitrobenzyl alcohol gives p-nitrobenzaldehyde in the catalytic oxidation system.23c Oxygen can be used6 as the stoichiometric oxidant.

Catechols, hydroquinones, and their methyl ethers readily afford quinones on CeIV oxidation.4,24 Partial demethylative oxidation is feasible, as shown in the preparation of several intramolecular quinhydrones (eq 5)25 and a precursor of daunomycinone.26 Sometimes the dual oxidant system of CAN-NaBrO3 is useful. In a synthesis of methoxatin (eq 6)27 the o-quinone moiety was generated from an aryl methyl ether.

Oxidative regeneration of the carboxylic acid from its 2,6-di-t-butyl-4-methoxyphenyl ester28 is the basis for the use of this auxiliary in a stereoselective a-hydroxyalkylation of carboxylic acids. The smooth removal of p-anisyl (eq 7)29 and p-anisylmethyl30 groups from an amidic nitrogen atom by CeIV oxidation makes these protective groups valuable in synthesis.

Simple ethers are oxidized31 to carbonyl products and the intermediate from tetrahydrofuran oxidation can be trapped by alcohols.32

Vicinal diols undergo oxidative cleavage.33 There is no apparent steric limitation as both cis- and trans-cycloalkane-1,2-diols are susceptible to cleavage. However, under certain conditions a-hydroxy ketones may be oxidized without breaking the C-C bond.6

Oxidation of Carbonyl Compounds.

The CeIV oxidation of aldehydes and ketones is of much less synthetic significance than methods using other reagents. However, cage ketones often provide lactones (eq 8)34,35 in good yield. Tetracyclones furnish a-pyrones.36

Concerning carboxylic acids and their derivatives, transformations of practical value are restricted to oxidative hydrolysis such as the conversion of hydrazides37 back to carboxylic acids, transamidation of N-acyl-5,6-dihydrophenanthridines,38 and decarboxylative processes, especially the degradation of a-hydroxymalonic acids (eq 9).39 In some cases the CeIV oxidation is much superior to periodate cleavage. A related reaction is involved in a route to lactones.40

Nitrogenous derivatives of carbonyl compounds such as oximes and semicarbazones are oxidatively cleaved by CeIV,41 but only a few synthetic applications have been reported.42

Oxidation of Nitroalkanes.

CeIV oxidation provides an alternative to the Nef reaction.43 At least in the case of a ketomacrolide synthesis (eq 10),44 complications arising from side reactions caused by other reagents are avoided.

Oxidation of Organosulfur Compounds.

Thiols are converted into disulfides using reagents such as Bis[trinitratocerium(IV)] Chromate.45 Chemoselective oxidation of sulfides by CeIV reagents to sulfoxides4,46 is easily accomplished. Stoichiometric oxidation under phase transfer conditions46b and the dual oxidant4 protocols permit oxidation of a variety of sulfides.

The reaction of dithioacetals including 1,3-dithiolanes and 1,3-dithianes with CAN provides a convenient procedure for the generation of the corresponding carbonyl group.47 The rapid reaction is serviceable in many systems and superior to other methods, e.g. in the synthesis of acylsilanes.48 In a series of compounds in which the dithiolane group is sterically hindered, the reaction led to enones, i.e. dehydrogenation accompanied the deprotection (eq 11).49

Oxidative Cleavage of Organometallic Compounds.

Oxidative deligation of both s- and p-complexes by treatment with CAN is common practice. Ligands including cyclobutadiene and derivatives (eq 12)50 and a-methylene-g-butyrolactone (eq 13)51 have been liberated successfully and applied to achieving the intended research goals. In the recovery of organic products from a Dötz reaction, CAN is often employed to cleave off the metallic species.52

Generation of a-Acyl Radicals.

As a one-electron oxidant, CeIV can promote the formation of radicals from carbonyl compounds. In the presence of interceptors such as butadiene and alkenyl acetates, the a-acyl radicals undergo addition.53 The carbonyl compounds may be introduced as enol silyl ethers, and the oxidative coupling of two such ethers may be accomplished.54 Some differences in the efficiency for oxidative cyclization of d,ε-, and ε,ζ-unsaturated enol silyl ethers using CAN and other oxidants have been noted (eq 14).55

Oxidative Halogenation.

Benzylic bromination56 and a-iodination of ketones3a and uracil derivatives3b can be achieved with CAN as in situ oxidant.

Related Reagents.

Cerium(IV) Ammonium Nitrate-Sodium Bromate; Iodine-Cerium(IV) Ammonium Nitrate.

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Tse-Lok Ho

National Chiao-Tung University, Hsinchu, Taiwan, Republic of China

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