Highly Efficient Formation of Nitriles and Alkoxy Radicals from N-Alkoxybenziminoyl Chlorides in Solution

Abstract

A series of N-alkoxybenziminoyl chlorides were synthesized and reacted with tributyltin hydride in the presence of AIBN to generate the corresponding N-alkoxybenziminoyl radicals. This methodology successfully generates the desired radicals, which undergo a rapid and highly efficient β-scission reaction, as shown by the formation of the corresponding nitriles and products derived from alkoxy radicals. The intermediate N-alkoxybenziminoyl radical could not be trapped by employing high concentrations of Bu3SnH or by using a hydrogen atom donating solvent such as toluene. The fast β-scission reaction was found to be independent of the structure of the iminoyl chloride. These results are different from studies on the similar N-alkyliminoyl radicals, which typically give products from both β-scission hydrogen atom transfer pathways. Using the data from this study as well as some reported rate constants for different hydrogen atom transfer (HAT) processes, we conclude that the lower limit for the rate constant for the β-scission process (k β) in N-alkoxybenziminoyl radicals is 2.5 × 107 s−1.

Mechanistic Investigation of the Formation of Isoindole N-Oxides in the Electron Transfer-Mediated Oxidative Cyclization of 2′-Alkynylacetophenone Oximes

“…When the reaction was done with chloranil (CA) as the sensitizer at 350 nm (entry 2), the only reactivity observed was E / Z isomerization (as confirmed by the same reaction without CA present). Previously, we have observed that reactions of oximes and oxime ethers derived from aldehydes react slower than those derived from ketones. − Our next step, therefore, was to look at the reactivity of the corresponding acetophenone oxime ether ( 2 ). Reacting oxime ether 2 with DCA at 420 nm (entry 4) did not result in any significant product formation; again, degradation of the starting material was the main pathway.…”

“…To promote formation of the iminoxyl radicals, the reactions were carried out with chloranil (CA) as the sensitizer. The CA radical anion is known to be basic, − and spectroscopic studies have shown the formation of the semiquinone radical via proton transfer from an oxime radical cation to the CA radical anion . Irradiation of oxime 3 at 350 nm in the presence of CA (Table , entry 7) resulted in the formation of new signals in the NMR spectrum.…”

“…Oxime-derived compounds have a broad range of applications such as industrial chemicals, − pharmaceuticals, − and antidotes for nerve gas poisoning. − Because oximes and oxime ethers contain two heteroatoms, they are popular reagents for the synthesis of heterocycles, including natural products and pharmaceuticals via intermolecular and intramolecular reactions. − We have previously reported on the use of 2′-arylbenzaldehyde oxime ethers as precursors for the synthesis of phenanthridine derivatives under photoinduced electron transfer (PET) conditions . This work was based on the observation that oxime ether radical cations underwent intermolecular nucleophilic attack at the nitrogen, whereas oximes did not show such reactivity but instead formed the corresponding carbonyl or nitrile via the proposed iminoxyl or iminoyl radicals. , The intermediate oxime radical cations are highly acidic and quickly lose a proton to form an iminoxyl radical, which might be more prone to react with a built-in radical trap. ,, Our initial study on the oxidative cyclization reactions of oximes and oxime ethers showed that built-in aromatic rings behaved as nucleophiles reacting with the nitrogen atom of the oxime ether moiety . Because the oximes did not show such reactivity, it was proposed that aromatic rings do not act as radical traps.…”

“…22 This work was based on the observation that oxime ether radical cations underwent intermolecular nucleophilic attack at the nitrogen, 23 whereas oximes did not show such reactivity but instead formed the corresponding carbonyl or nitrile via the proposed iminoxyl or iminoyl radicals. 24,25 The intermediate oxime radical cations are highly acidic and quickly lose a proton to form an iminoxyl radical, which might be more prone to react with a built-in radical trap. 22,26,27 Our initial study on the oxidative cyclization reactions of oximes and oxime ethers showed that built-in aromatic rings behaved as nucleophiles reacting with the nitrogen atom of the oxime ether moiety.…”

Catalytic Oxidative Cyclization of 2′-Arylbenzaldehyde Oxime Ethers under Photoinduced Electron Transfer Conditions

“…6 The nitriles were proposed to result from intermediate imidoyl radicals, which are formed via hydrogen atom abstraction at the iminyl carbon (Scheme 1). 7 …”