Amines dimethyldioxirane

In general, peroxomonosulfates have fewer uses in organic chemistry than peroxodisulfates. However, the triple salt is used for oxidizing ketones (qv) to dioxiranes (7) (71,72), which in turn are useful oxidants in organic chemistry. Acetone in water is oxidized by triple salt to dimethyldioxirane, which in turn oxidizes alkenes to epoxides, polycycHc aromatic hydrocarbons to oxides and diones, amines to nitro compounds, sulfides to sulfoxides, phosphines to phosphine oxides, and alkanes to alcohols or carbonyl compounds. 

The most widely employed methods for the synthesis of nitrones are the condensation of carbonyl compounds with A-hydroxylamines5 and the oxidation of A+V-di substituted hydroxylamines.5 9 Practical and reliable methods for the oxidation of more easily available secondary amines have become available only recently.10 11 12 13. These include reactions with stoichiometric oxidants not readily available, such as dimethyldioxirane10 or A-phenylsulfonyl-C-phenyloxaziridine,11 and oxidations with hydrogen peroxide catalyzed by Na2W044 12 or Se02.13 All these methods suffer from limitations in scope and substrate tolerance. For example, oxidations with dimethyldioxirane seem to be limited to arylmethanamines and the above mentioned catalytic oxidations have been reported (and we have experienced as well) to give... 

Secondary amines (R2NH) are oxidized to hydroxylamines (R2NHOH), which are resistant to further oxidation, by dimethyldioxirane and by benzoyl peroxide and NajHPOa. " ... 

Aliphatic and aromatic primary amines are rapidly and efficiently oxidized to nitro compounds by dimethyldioxirane.111 Dimethyldioxirane is prepared by reaction of OXONE (DuPont trademark)-2KHS05-KHS04-K2S04 with buffered aqueous acetone.112... 

In a typical reaction, w-butylamine (0.052 g, 0.7 mmol) in 5 ml of acetone is treated with 95 ml of dimethyldioxirane in acetone solution (0.05 M). The solution is kept at room temperature for 30 min with the exclusion of light (Eq. 2.53). Aromatic amines are converted into nitro compounds by oxidation using OXONE itself.113... 

Aromatic amines are oxidized by Oxone in acetone to produce the corresponding nitro arenes in good to high yield (50-100%) [12]. The reaction is thought to proceed via the initial formation of dimethyldioxirane. Electron excessive heteroarenes, which are normally very susceptible to oxidation are untouched by the reaction. 

Polymer-supported permthenate has also been used in two convergent pathways for the synthesis of isoxazoUdines with each route employing different starting materials in order to create the maximum structural diversity [73]. In the first route secondary hydroxylamines, readily prepared from amines by in situ treatment with dimethyldioxirane, were oxidized directly to nitrones using polymer-supported permthenate (PSP). Alternatively, primary alcohols were used as the... 

Primary, secondary and tertiary aliphatic amines are efficiently converted to nitro compounds in 80-90 % yield with dimethyldioxirane, a reagent prepared from the reaction of oxone (2KHSO5-KHSO4-K2SO4) with buffered acetone. Dimethyldioxirane (DMDO) has been used for the synthesis of 1,3,5,7-tetranitroadamantane (71) from the corresponding tetraamine as the tetrahydrochloride salt (70) and is an improvement over the initial synthesis using permanganate anion (Table 1.7). ° Oxone is able to directly convert some aromatic amines into nitro compounds. 

Dimethyldioxirane was reported to provide superior yields of hydroxylamines in comparison to other peroxide oxidizing agents. This reaction worked well on polyfunctional amines such as O-protected aminosaccarides 140 (equation 94), yet it was found to be substrate-sensitive and failed to provide hydroxylamines in several cases . 

Tertiary alkyl primary amines can be oxidized to nitro compounds in excellent yields with KMn04.39S This type of nitro compound is not easily prepared in other ways. All classes of primary amine (including primary, secondary, and tertiary alkyl as well as aryl) are oxidized to nitro compounds in high yields with dimethyldioxirane.399 Other reagents that oxidize various types of primary amines to nitro compounds are dry ozone,4,111 various peracids,401 including peracetic and peroxytrifluoroacetic acids, f-butyl hydroperoxide in the presence of certain molybdenum and vanadium compounds,402 F7-H20-MeCN,41123 and sodium perborate.403... 

Tertiary amine oxides can be converted into TV-hydroxy secondary amines provided that one of the TV-substituents can be selectively eliminated. This procedure has been applied to the synthesis of secondary A-hydroxy-a-amino acids 34 from the corresponding secondary a-amino acids using the /V-cyanoethyl group for transient protection of the secondary amine (Scheme 10) J40l More recently, direct oxidation with 2,2-dimethyldioxirane of a primary amine has been described for H-L-Val-OMe (82% yield) and H-L-Phe-OMe (54% yield))13 The reaction proceeds smoothly without epimerization, but no experimental details have been reported. 

RNH2 —> RN02.3 Dimethyldioxirane oxidizes aliphatic or aromatic amines to nitro compounds in 85-97% yield, probably via the intermediates shown in equation (I). 

Methoxy-2,2,6,6-tetramethyl-1 -oxopiperidinium chloride, 183 Pyridinium chlorochromate-Benzotria-zole, 262 of amines to nitro compounds Dimethyldioxirane, 120 other nitrogen compounds /-Butyl hydroperoxide-Dichlorotris-(triphenylphosphine)ruthe-nium(II), 54 Di-/-butylimoxyl, 94 Potassium ruthenate, 259 Ruthenium tetroxide, 268 of aromatic side chains Trimethylsilyl chlorochromate, 327 of diols... 

AMI and PM3 calculations reveal that epoxidations by DMDO and TFDO involve peroxide-bond cr at a very early stage and that TFDO is the most reactive dioxirane as the CF3 group in it stabilizes this cr level. In accord with previous calculations a spiro transition state is predicted. Furthermore, allene is predicted to be less reactive than alkenes toward epoxidation by DMDO.192 DFT calculations on the oxidation of primary amines by dimethyldioxirane predict a late transition state with a barrier of 17.7 kcal mol-1 which is drastically lowered by hydrogen bonding to the O—O bond to just 1.3 kcal mol-1 in protic solvents.193... 

Oxidation. Benzylic secondary amines are oxidized in high yield by dimethyldioxirane to nitrones,1 probably via hydroxylamines.2... 

Nitroxides,5 Cyclic secondary amines are oxidized by dimethyldioxirane (1) to nitroxides in yields >95%. 

Dimethyldioxirane oxidizes primary amines to nitro compounds either preformed349 in acetone or in situ.350... 

Dimethyldioxirane (1) is a mild and efficient oxidant for pyridine pyiidines and quinolines have also been oxidized in good yield by r-pentylhydroperoxide in the presence of molybdenum(V) chloride. A(-Halogenation and other oxidative reactions of pyridines and related heterocycles have been re-viewed. " Thus, pyridines and some diazines can be aminated by mesitylenesulfonylhydtoxylamine... 

AIBN = 2,2 -azobisisobutyronitrile 9-BBN = 9-borabicyclo [3.3.1]nonane Bn = benzyl BOC = f-butoxycarbonyl Bz = benzoyl CAN = ceric anunoninm nitrate Cp = cyclopenta-dienyl Cy = cyclohexyl DAST = diethylaminosnllur trifln-oride DBA = l,3-dibromo-5,5-dttnethylhydantoin DDQ = 2,3-dichloro-5,6-dicyano-l,4-benzoquinone DET = diethyl tartrate DIAD = diisopropyl acetylene dicarboxylate DIBAL-H = diisobutylalummum hydride DIPEA = diisopropyl ethyl amine DMDO = dimethyldioxirane HMPA = hexamethylphosphortriamide EDA = lithium diisopropy-lamide Ms = methylsulfonyl MOM = methoxymethyl NBS = iV-bromosuccmimide NMO = A-methylmorpholine iV-oxide PDC = pyridinium dichromate PMP = p-methoxyphenyl THP = tetrahydropyranyl TIPS = trisiso-propylsilyl TMANO = trimethylamine A-oxide TBDMS = t-butyldimethylsilyl Tf = trifluoromethanesulfonyl TMP = 2,2,6,6-tetramethylpiperidyl TMS = trimethylsilyl Ts = p-toluenesulfonyl. 

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 dimethyldioxirane (1). ... 

The nucleophilic substitution, amination, aldol-type condensation, oxidation, and hydrolysis of the l//-pyrazino[2,3-c][l,2,6]thiadiazine 2,2-dioxide system, structurally related to pteridine, were studied in detail <03HCA139>. Chlorinated pyrazines were directly oxidized to their corresponding iV-oxides using dimethyldioxirane in a completely regioselective fashion <03HEC221 >. 1,6-Dibenzoyl-5//, 10//-diimidazo[ 1,5-a 1, 5 -[Pg.374]

Dimethyldioxirane (52) and other methyldioxiranes are easily generated peroxides which have proved to be very useful oxygen atom transfer agents alkenes, sulfides and amines can all be oxidized and dimethyldioxirane is reduced to acetone. ... 

Dioxiranes, three-membered-ring cyclic peroxides, are known as highly efficient and selective oxidants, capable of performing a variety of transformations for synthetic purposes. It is known that some reactions of these peroxides are accompanied by chemiluminescence due to the release of singlet oxygen. For instance, infra-red chemiluminescence (IR-CL) of O2 at A, 1270 nm is emitted in the reaction of tertiary amines and N-oxides with dimethyldioxirane (DMD) and methyl(trifluoromethyl)dioxirane (TFD), as well as during the anion-catalyzed breakdown of the dioxiranes. Furthermore, IR-CL emission is produced in the ketone-catalyzed decomposition of the monoperoxysulfate ion HSOs through the intermediary dioxirane. ... 

The oxidation of organic compounds with dioxirane reagents has emerged as an important synthetic method [93,94,95]. The effective use of dimethyldioxirane and methyl(trifluoromethyl)dioxirane for the mild and efficient oxidation of olefins, sulfides, amines, and saturated hydrocarbons naturally raised the question whether chiral versions of these reagents can be developed. 

---