Mechanisms of the C-H halogenation of adamantane in the presence of N-hydroxyphthalimide

Abstract

A study was carried out on the mechanisms for the halogenation of the C-H bonds in systems containing oxone, and CHal 4 or N-hydroxyphthalimide and t-BuOCl. These reactions proceed with the participation of the phthalimido-N-oxyl (PINO) radical, which may serve either as an initiator or reagent. A DFT (density functional theory) model showed that the PINO radical may be generated efficiently in the presence of t-BuOCl as the initiator.Alkanes are the most available organic compounds but their use in fine chemical synthesis is extremely limited. Saturated hydrocarbons react readily with radicals but the selectivity of their transformations is insufficient for use in preparative chemistry. Oxygen radicals such as hydroxyl and alkoxyl species are often employed in the radical transformations of alkanes. The hydroxyl radical is extremely reactive but lacks selectivity in the replacement of C-H bonds. The bulky and less reactive tert-butoxyl radical displays higher selectivity. Although the use of such radicals permits some improvement in the selectivity in the reactions of alkanes, further progress has been achieved by the use of electrophilic radicals such as NO 3 ⋅ , NO 2 ⋅ , TEMPO, and succinimidyl, which are more selective toward polar effects.Special interest is found in the phthalimido-N-oxyl (PINO ⋅ ) radical, which displays high selectivity in reactions with alkanes and is conveniently generated in situ from N-hydroxyphthalimide (NHPI) in the presence of oxidizing agents [1]. Typical systems for the generation of PINO ⋅ involve either transition metals such as NHPI/O 2 /Co(acac) 2 [2] and NHPI/CAN (cerium ammonium nitrate) or strong inorganic oxidizing agents (usually nitrogen-containing compounds [3]). The participation of PINO ⋅ in the abstraction of a hydrogen atom from a hydrocarbon selectively yields ketones, alcohols, carboxylic acids, and other derivatives in good yield [3][4][5][6].Since a series of other nonalkyl radicals also arise in the generation of PINO ⋅ , any of which might participate in the activation of the C-H bond, the mechanisms for the functionalization of hydrocarbons in the presence of NHPI have not been readily elucidated. Figure 1a gives a generalized mechanism for the functionalization of alkanes R-H in the presence of PINO ⋅ . The action of an initiator In ⋅ (nitrogen oxides, peroxide radicals, formed from oxygen in the presence of transition metals) on NHPI gives the PINO ⋅ radical, which abstracts a hydrogen atom from the R-H molecule to give an alkyl radical, 48 0040-5760/08/4401-0048

Mild Aliphatic and Benzylic Hydrocarbon C–H Bond Chlorination Using Trichloroisocyanuric Acid

“…In continuation of our previous studies on C–H bond halogenations, we herein report a safe, cheap, atom-economic, air- and moisture-tolerating approach for the side-chain chlorination of a range of arenes and alkanes with yields (of isolated product) of up to 85% at 25–30 °C with N -hydroxyphthalimide 1 (NHPI) as radical initiator. …”

The Halogenation of Aliphatic C-H Bonds with Peracetic Acid and Halide Salts

“…19 Our process has four benefits over most previously reported halogenation reactions. 9,[25][26][27] First, PA is a relatively innocuous terminal oxidant, particularly compared to the more commonly used Cl 2 and Br 2 . 9,27 Second, the halogen source is a halide salt, as opposed to an elemental halogen or a halogenated solvent, such as chloroform or carbon tetrachloride.…”

“…25 Third, the reported halogenation requires neither high temperatures nor a heavy-metal catalyst to proceed. 26 Fourth, the PA-mediated halogenation can be adapted to work in water. Despite the relatively mild conditions, the reaction can activate strong aliphatic C-H groups, such as the 95-100 kcal mol -1 bonds found in cyclohexane.…”

Theoretical study on the catalytic reactivity of N-hydroxyphthalimide tuned by different heterocyclic substitutions on its phenyl ring for aerobic oxidation

“…The H-abstraction reactions by PINO Å from toluene with electron-donating substituents [17] or by the derivatives of PINO Å with electronwithdrawing substituents from cyclohexene [18] can be largely favored, which have been experimentally supported. Besides, the selective oxidation mechanisms of isophorones catalyzed by NHPI [12], the promotion effect of t-BuOCl on the generation of PINO Å from NHPI [26], and the facile decomposition routes of hydroperoxides to ketones by nitroxy radicals [27] were systemically elucidated theoretically. Furthermore, the experimentally observed higher catalytic efficiencies of multi-nitroxyl catalysts than that of NHPI have been rationalized as the stronger electron-withdrawing effects involving in their special nitroxy radicals [19,20].…”