Convenient oxidation of benzylic and allylic halides to aldehydes and ketones

Abstract

Benzylic and allylic halides were conveniently oxidized to aldehydes and ketones by pyridine Noxide in the presence of silver oxide under mild conditions. Aldehydes and ketones, especially aromatic and α,β-unsaturated carbonyl compounds, are important classes of chemicals. Methods for direct conversion of halides to carbonyl compounds have been reviewed. 1,2 Dimethyl sulfoxide (DMSO) is often employed as the oxygen donor. 3,4 However, high temperature is usually required. 3,4 Oxidations involving amine oxides have also been reported. [5][6][7] In our attempt to modify carbohydrates with benzylic halides, we have found that pyridine N-oxide can effectively and conveniently oxidize benzylic and allylic halides to aromatic and α,β-unsaturated carbonyl compounds, respectively, in the presence of silver oxide (Ag 2 O) under mild conditions. 8,9The reactions were carried out in acetonitrile (toluene and tetrahydrofuran gave much lower yield). The reaction mechanism should be identical to that proposed for the reaction with DMSO and base, as shown in Scheme 1. 1,8 Half equivalent of silver oxide was utilized to facilitate the reaction. Silver oxide assists the heterolysis of the carbon-halogen bond in the substitution reaction with pyridine N-oxide. The resulting hydroxide ion from the reaction between silver oxide and halogen then functions as the base in the elimination reaction to produce the carbonyl group. When DMSO was employed instead of pyridine N-oxide as the source of oxygen, the reaction did not go to completion while giving a mixture of products.For most bromides, the reactions were conveniently carried out at room temperature. The reaction was complete in a few hours but was stirred overnight for convenience. For chlorides and some benzyl bromides with very strong electron-withdrawing substituents, slightly elevated temperature (50 °C) was required (Entries 4-7 and 12-15 in Table 1). For some chlorides, only partial conversion was observed (Entries 13 and 14). The substituent effects indicate a S N 1-like mechanism for the first step in the reaction pathway.The reaction workup was very simple. Upon completion of the reaction, sodium sulfate or magnesium sulfate was added and the resulting mixture was filtered through a thin layer of Celite. Concentration of the filtrate gave essentially pure product in quantitative yield. 10

A New Pyrimidine Schiff Base with Selective Activities against Enterococcus faecalis and Gastric Adenocarcinoma

“…It appears that the formation of imine 3 as a byproduct during the reaction of chloromethylpyrimidine 1 and p -phenetidine can be linked with redox properties of the products of oxidation of p -phenetidine. There are known reactions that exploit N -oxides of amines, such as pyridine N-oxides [ 58 , 59 , 60 ] or another tertiary amine N -oxides [ 61 , 62 ], for the conversion of chlorides into aldehydes. On the other hand, p -phenetidine is suggested to form 4-(ethoxyphenyl)- p -benzoquinone imine (4-EPPBQI) as a major product of its oxidation ( Scheme 2 ) [ 63 , 64 ].…”

Convenient one-pot synthesis of trans-1,2-diaryloxiranes from the direct coupling of benzyl halides

“…Previously we reported a convenient method for the conversion of benzyl halides to aldehydes and ketones in the presence of Ag 2 O and pyridine N-oxide 4. When DMSO was employed instead of pyridine N-oxide as the source of oxygen, it was noted that reaction with benzyl bromide gave a mixture of products 4.…”

“…When DMSO was employed instead of pyridine N-oxide as the source of oxygen, it was noted that reaction with benzyl bromide gave a mixture of products 4. An epoxide, trans -stilbene oxide, was isolated from the product mixture.…”

Oxidation of Benzyl Halides and Related Compounds to Carbonyl Compounds Using Hydrogen Peroxide Catalysed by Tempo in Water

“…Many successful methods have been developed for the direct conversion. The Krohnke reaction, 1 the Kornblum reaction [2][3][4] and a number of its variants, [5][6][7] copper(I) chloride/Kieselguhr, 8 selenium compounds, 9 IBX, 10 K 2 CO 3 /DMSO, 11 MnO 2 , 12 Bi(NO 3 ) 3 .5H 2 O/TBAF, 13 NaIO 4 /DMF, 14 pyridine N-oxide, 15 NaIO 4 , 16 V 2 O 5 /Aliquat 336/H 2 O 2 , 17 bromate exchange resin, 18 3,6-bis(triphenylphosphonium)cyclohexene peroxodisulfate, 19 and Mg-Al hydrotalcites/DMSO 20 have been developed for this transformation. These oxidation systems are quite useful for small-scale reactions, but, most of these methods require hazardous, expensive or toxic reagents or high reaction temperatures for long reaction times.…”