Cleavage of the N–O bond in substituted hydroxylamines under basic conditions Kirill V. Nikitin* and Nonna P. Andryukhova Department of Chemistry, M. V. Lomonosov Moscow State University, 119899 Moscow, Russian Federation. Fax: +7 095 939 0798; e-mail: newscientist@mtu-net.ru DOI: 10.1070/MC2000v010n01ABEH001206 The cleavage of the N–O bond in hydroxylamines R 1 NR–OR 2 accompanied by oxidation of the adjacent carbon is directed by the CH acidity of R 1 and R 2 groups. Oxidation by organic amine oxides has been effectively em- ployed 1–3 to convert organic halides (Scheme 1) into corre- sponding aldehydes. In these methods, the aldehyde oxygen comes from the amine oxide used as an oxidant 1 so that, in the intermediate, the carbon atom adjacent to the oxygen atom is oxidised. Similarly, the oxidation at carbon atom in the 3-posi- tion of isoxazoles 4 and the oxidative rearrangement of isoxazol- 3-ones 5 have been reported. To our knowledge, the tendencies for N–O cleavage in hydroxylamines R 1 NR–O R 2 1 have not been studied under basic conditions although similar N–O bond reductive cleavage can be expected via an intermediate carbanion. We studied the behaviour of 1 under basic conditions (Et 3 N, NaOMe, NaH or LDA in THF). In a series of substrates we tried to arrange the substituents around the N–O m oiety in order to favour the formation of a carbanion adjacent to oxygen or nitrogen. The results are summarised in Table 1. We observed differences in the behaviour of mono- (1a), di- (1b) and tribenzylhydroxylamine (1c). While 1a (Table 1, run 1) is apparently converted by sodium hydride to benzalde- hyde (Scheme 2), and the latter is condensed with an excess of unreacted 1a into the final product O-benzylbenzaldoxime, 1b and 1c unexpectedly do not undergo any transformations under the same conditions (runs 2 and 3). The difference may be ac- counted for by the lower CH acidity of methylene in 1b and 1c. Benzoyloxyphthalimide 1d does not react with weak bases such as triethylamine (Table 1, run 4) or strong bases (sodium hydride, run 5). With sodium ethoxide (run 7) or lithium diiso- propylamide (run 6), ring opening takes place. Thus, the acidity of the benzylic methylene in 1b–d is insufficient to provide a carbanion for further transformations though the nitrogen is in- volved into the electron-withdrawing phthalimide system. N-Benzoyloxy- -phenylethylamine 1e benzoylated at the oxy- gen atom has only one possibility to form a carbanion capable of N–O cleavage. Under basic conditions, 1e is slowly converted (Table 1, run 8) into acetophenone and acetophenone oxime (after treatment with water). Since the introduction of a carbonyl group should increase drastically the acidity of the -methylene adjacent to the oxygen atom, we tested the behaviour of N-benzoylmethoxyphthalimide 1f. We found that 1f can be easily converted into phthalimide with a catalytic amount of sodium hydride (Table 1, run 9); the products of benzoylmethoxy group degradation were not iden- tified. Similarly, N-benzoylmethoxy-N-(1-phenylethyl)phenyl- acetamide 1g and N-benzoylmethoxy-N-tert-butylphenylacet- amide 1h undergo transformations leading to the corresponding amides in high yields (runs 10 and 11). The possible base cata- lysed mechanism involves the formation of a methylene carb- anion followed by N–O bond cleavage (Scheme 3). In the last example, 1-benzyl-5-benzyloxyamino-3,4-dimethyl- pyrrolin-2-one 1i, the carbon atom adjacent to the N atom of the N–O system is a member of a pyrrolin-2-one ring. Apparently, the CH acidity at this atom is enough to allow intermediate carb- anion formation 6 (Scheme 4) leading quantitatively to N–O cleav- age products (Table 1, run 12). Thus, the cleavage of the N–O bond in 1 under basic con- ditions is directed by the formation of a carbanion centre adjacent to either nitrogen or oxygen atom. The structures in which a carbanion can be formed near nitrogen undergo reduction of the N–O with the release of R 2 O – as a leaving group and formation of an imine. Similarly, if a carbanion is situated near oxygen, the cleavage leads to RR 1 N – and an aldehyde. References 1 A. G. Godfrey and B. Ganem, Tetrahedron Lett., 1990, 31, 4825. 2 V. Franzen and S. Otto, Chem. Ber ., 1961, 1363. 3 D. Barby and P. Champagne, Tetrahedron Lett., 1996, 37, 7725. 4 E. Dominiguez, E. Ibeas, E. Martines, J. K. Palacios and R. San Martin J. Org. Chem., 1996, 61, 5435. 5 H. Uno and M. Kurokawa, Chem. Pharm. Bull., 1978, 26, 549. 6 K. V. Nikitin and N. P. Andryukhova, Mendeleev Commun., 1999, 168. RCH 2 X RCH 2 ONMe 3 RCHO Me 3 NO Scheme 1 PhCH 2 ONH 2 PhCHO PhCHNOCH 2 Ph NaH Scheme 2 1a 1a N O Ph O O Ph N O Ph O HC O Ph N Ph O NaH 1g Ph Ph Ph Scheme 3 N O HN O CH 2 Ph Ph 1i C N O HN O CH 2 Ph Ph N O NH Ph NaH Scheme 4 Received: 21st September 1999; Com. 99/1534 Mendeleev Commun., 2000, 10(1), 32–33 – 32 –