Amines oxidation with MCPBA

Tlie isolable dithiiranes (4 and 7) are fairly stable under acidic conditions but quickly lose a sulfur atom to give the corresponding thioketones under basic conditions (97BCJ509). Tliey are quite sensitive toward amines and phosphines. Oxidation with MCPBA gave the corresponding dithiirane 1-oxides in high yields. 

When the unsaturated tertiary amine, pitprofen (179 R = H) is treated with MCPBA the reaction takes place selectively at the mwe nucleophilic nitrogen to furnish the corresponding amine oxide with the alkene moiety intact. In contrast, peroxycarboximidic acid, prepared in situ from acetonitrile/H202. reacts selectively with the alkene moiety of the ester (179 R = Me equation 65). The sterically hindered nitrogen of (179) is able to react with peroxy acids which have a low steric demand, but not with peroxy-caiixrximidic acids which have a large steric demand. 

Amine protection. Primary and secondary amines are protected as r-butylsulfonamides by reaction with f-BuS(=0)Cl followed by oxidation with MCPBA. These derivatives are stable to strong bases including those used for metallation. However, they are cleaved by acid. 

Oxidation with mCPBA Nucleophilic aromatic [22-28] or oxone substitution with amines... 

Like 2-aminopyridines and 2-aminopyrimidine, 2-aminopyrazine (39) (Scheme 29) has been converted into the nitroso compound (121) by reaction with dimethyl sulfide and NCS followed by deprotonation of the resulting sulfonium salt with sodium methoxide to the 5, 5-dimethylsulfilimine and then oxidation with MCPBA <82JOC552>. The extremely reactive nitrosopyrazine (121) condenses with 1,3-dienes to give 3,6-dihydro-1,2-oxazines and with aromatic amines in the presence of acid to gives azo compounds, and is smoothly oxidized with ozone or sodium hypochlorite to 2-nitropyrazine (122). Methyl 3-aminopyrazinecarboxylate reacts with thiophosgene to produce the... 

A simple, efficient synthesis of 4-substituted 1,2,4,6-thiatriazine 1,1-dioxides involves reacting 0,0 -diaryl carbonimidates with thionyl chloride and triethylamine to give sulfoxides which are oxidized with MCPBA. The resulting sulfamides are then reacted with primary amines to give the required products (Scheme 9) <87S170>. 

Alternatively, sulfonamides can also be prepared by oxidation of sulfinamides with periodate (Entry 3, Table 8.8) or with MCPBA [125]. Polystyrene-bound sulfonyl chlorides, which can be prepared from polystyrene-bound sulfonic acids by treatment with PCI5, SOCI2 [126-129], CISO3H [130], or SO2CI2/PPI13 [131], react smoothly with amines to yield the corresponding sulfonamides (Entry 4, Table 8.8). Support-bound carbamates of primary aliphatic or aromatic amines can be N-sulfonylated in the presence of strong bases, and can therefore be used as backbone amide linkers for sulfonamides (Entries 5 and 6, Table 8.8). 

Treatment of A-methylaniline with 4-chlorobut-2-yn-l-ol in acetone at reflux temperature in the presence of anhydrous K2CO3 gave the expected tertiary amine in 91% yield. Room temperature oxidation of a dilute solution of this amine with MCPBA resulted in formation of a colourless crystalline solid in 56% yield, which was shown to have structure 1. 

Reaction of thiepine 26 with MCPBA in CH2CI2 gave sulfoxide 83 in 99% yield however, 83 did not react under various oxidizing conditions including mesitylenesulfonylhydroxylamine 84, which reacted with diphenyl sulfoxide to give aminated product (Equation 9) <20060BC2218>. 

A A -Disulfonamides are decomposed with sodium hydrogencaibonate in DMSO to give ketones. Imines formed from the reaction of primary amines with carbonyl compounds can be oxidized to ox-aziridines with MCPBA which hydrolyze to aldehydes or ketones with acid. When acetone is used, the final by-products are ammonia and acetone (equation 37). The use of 2-pyridinecarbaldehyde is preferred since it gives an acid-soluble by-product which aids work-up (equation 38)." ... 

Reactions which formally involve the oxidation of azides have been reviewed by Boyer. Other oxidations with useful synthetic applications include two which start from nitrogen ylides. Sulfimides (50) derived from electron-deficient aromatic and heterocyclic amines are oxidized to the corresponding nitroso compounds by MCPBA. - This is a very useful method of preparation of some otherwise inaccessible nitroso compounds such as 2-nitrosopyridine and 1-nitrosoisoquinoline. They can be further oxidized, for example by ozone, to the nitro compounds. Phosphimides (51) are oxidized directly by ozone to the nitro compounds, although the nitroso compounds are intermediates. Isocyanates can also be oxidized to the corresponding nitro compounds, by dimediyldioxiraiK (1). ... 

Nitrones, C=N" (R)=0, are generated by the oxidation of N-hydroxyl secondary amines with 5% aq. NaOCl. ° Secondary amines, such as dibenzylamine, can be converted to the corresponding nitrone by heating with cumyl hydroperoxide in the presence of a titanium catalyst. Imines are oxidized to amides with mcpba and BF3 OEt2. ° ... 

In their search for conformationally biased mimics of mannopyranosylamines, A. Vasella and co-workers planned to synthesize compounds that would inhibit p-mannosidases. In order to construct the bicyclo[3.1.0]hexane framework, a five-membered 0-silylated A/,A/-dimethyl-amino alcohol was synthesized. Oxidation of the tertiary amine with mCPBA yielded 83% of the A/-oxide, which was subsequently subjected to the Cope elimination to give 69% of the desired benzyl enol ether. Cyclopropanation of this enol ether gave rise to the highly functionalized bicyclic skeleton. 

Oxidation of sulfur compounds. Xanthates are converted to sulfines, and i-butylsulfmamides to sulfonamides. Thus, amines can be protected via sulfmylation, and the sulfonamides are cleaved by TFA or TfOH. Thiophene oxides are obtained when thiophenes are treated with MCPBA-BFj OEtj. ... 

Oxidation with H202 or Nucleophiles (hydroxides, [19-21] mCPBA amines)... 

The aza-Achmatowicz oxidation of (2-furylcarbinyl)amines continues to be a valuable method for the preparation of highly-substituted piperidines. The methoxy group in 150, prepared as shown in Scheme 61, underwent displacement reactions to provide useful carbon substituents, for example as a route to racemic azimic acid 151 <040L4029>. Treatment of 152 with mCPBA/DCM gave 153, presumably with maintenance of chiral integrity <04JOC2892>. 

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