Oxidation scheme

Sulfones and sulfoxides (145) are obtained usually from the corresponding sulfide by oxidation (Scheme 75) (341). though some of them were prepared from a halothiazole and metal sulfinate (342). 2-Amino-5-acetamidophenylsulfonylthiazole has been prepared by direct heterocycli-zation (343. 344). 

A very useful procedure for introducing a cyano group into a pyridazine ring is the Reissert-type reaction of the A/-oxide with cyanide ion in the presence of an acyl halide or dimethyl sulfate. The cyano group is introduced into the a-position with respect to the A-oxide function of the starting compound. The yields are, however, generally poor. In this way, 6-cyanopyridazines (111) can be obtained from the corresponding pyridazine 1-oxides (Scheme 33). 

Many pyrazine and quinoxaline syntheses yield mono- or di-N-oxides (76H(4)769). The condensation of a-aminooximes with 1,2-diketones results in the direct formation of pyrazine mono-N-oxides. The a-aminooximes themselves are not easily prepared but 2-amino-2-deoxy sugars readily form the oximes, which have been condensed with glyoxal to yield the pyrazine 4-oxides (Scheme 18) (72JOC2635, 80JOC1693). 

In spite of the usefulness of the Beirut reaction, mechanistically it is not well understood. It has been suggested that the first step involves the nucleophilic attack by the enolate or the enamine at N-3 of the benzofuroxan to yield an intermediate iV-oxide (Scheme 50) which subsequently undergoes tautomerism to an hydroxylamino derivative. This intermediate then cyclizes to the dihydroquinoxaline 1,4-dioxide. This suggestion has not been proven, and indeed there is evidence that benzofuroxan is in equilibrium with 1,2-dinitrosobenzene... 

Scheme 51), so it has been suggested that the initial reaction involves the dinitrosobenzene. It does seem, however, that this may be an over-simplification, as there are documented cases where mono-iV-oxides rather than the di-iV-oxides are formed for instance, the reaction of benzofuran-3(2//)-ones with benzofuroxan yields 3-(o-hydroxyphenyI)quinoxa-line 1-oxide (Scheme 52). Other mechanistic possibilities may also be put forward but it seems probable that more than one pathway may be operating, particularly in view of the more recent findings on the reactions of benzofuroxans (81AHC(29)251). 

Enamines and enolate anions react with benzofuroxan to give quinoxaline di-A -oxides (Scheme 38) (69AHC(10)1). Sydnones (274) with phenyl isocyanate give 1,2,4-triazoles (275) (76AHC(19)l), and from (276) the intermediate adduct (277) can be isolated (73JA8452). This is one of the few instances in which such primary cycloadducts have been isolated in the oxazole series of mesoionic compounds. 

Bromination of y-dinitrobutanoic acids and base treatment produced 3-nitroisoxazoline A-oxides (Scheme 139) (75MIP41601). Alkylation of the potassium salt of y-dinitro-2-butenoic acid also gave a similar compound (Scheme 139) (74KGS571). 

Attempted alkylation of methyl nitroacetate in base produced an isoxazoline Af-oxide (Scheme 140) (74CPB477), and the enamine (497) gave an isoxazoline A-oxide when reacted with methyl nitroacetate (74IZV845, 74MI41605). 

Dicarbonylimidazole reacted with the anthranilic acid derivative (498) to produce the fused isoxazolone IV-oxide (499) (77ZOR462). Methyl nitroacetate reacted with indole-3-carbaldehyde to produce (500) (70KGS1505). Treatment of (501) with base gave 3,4,5-triphenyl-2-isoxazoline IV-oxide (Scheme 142) (69JOC984). The reaction was reported to be a direct displacement as (502) did not give a product and no incorporation of deuterium was found using DOMe. 

The reaction of vinylogous amides, or ketoaldehydes, with hydroxylamine produced 4,5,6,7-tetrahydro-l,2-benzisoxazole. A side product is the 2,1-benzisoxazole (Scheme 173) (67AHC(8)277). The ring system can also be prepared by the reaction of cyclohexanone enamines with nitrile oxides (Scheme 173) (78S43, 74KGS901). Base treatment produced ring fission products and photolysis resulted in isomerization to benzoxazoles (76JOC13). 

The conversion of an alkene to an oxirane by an electrophilic oxidant (Scheme 72) is the commonest route to oxiranes (81H(15)517). The usual laboratory reagent is a peroxy acid... 

An interesting reaction is the ring enlargement (with rearrangement) caused by primary, but not secondary, amines with appropriately substituted 2-chloromethylquinazoline 3-oxides (Scheme 5). 

Song and Roh investigated the epoxidation of compounds such as 2,2-dimethylchromene with a chiral Mn (salen) complex (Jacobsen catalyst) in a mixture of [BMIM][PFg] and CH2CI2 (1 4 v/v), using NaOCl as the oxidant (Scheme 5.2-12) [62]. 

The reactions of arenediazonium ions with 7V-alkyl- or 7V-arylhydroxylamines were investigated by Bamberger (1920b, and earlier papers). Mitsuhashi et al. (1965) showed that the l,3-diaryl-3-hydroxytriazenes are tautomeric with 1,3-diaryltriazene-3-oxides (Scheme 6-16). Oxidation of 1,3-diaryltriazenes with peroxybenzoic acid in ether yields the same product as that from diazonium salts and TV-arylhydroxyl-amine. The infrared spectrum of the product obtained by coupling diazotized relabeled aniline with A/-phenylhydroxylamine indicates that the diaryltriazene-oxide is the preponderant tautomer. 

P-coupling occurs in the formation of azophosphonic esters [ArN2PO(OCH3)2] from diazonium salts and dimethyl phosphite [HPO(OCH3)2] (Suckfull and Hau-brich, 1958). P-coupled intermediates are formed in the reaction between diazonium salts and tertiary phosphines, studied by Horner and Stohr (1953), and by Horner and Hoffmann (1956). The P-azo compound is hydrolyzed to triphenylphosphine oxide, but if a second equivalent of the tertiary phosphine is available, phenyl-hydrazine is finally obtained along with the phosphine oxide (Scheme 6-26 Horner and Hoffmann, 1958). It is likely that an aryldiazene (ArN = NH) is an intermediate in the hydrolysis step of the P-azo compounds. 

The one-pot MCR of methylene active nitriles 47 has been used in the synthesis of both pyrano- and pyrido[2,3-d]pyrimidine-2,4-diones in a single-mode microwave reactor [90]. Microwave irradiation of either barbituric acids 61 or 6-amino- or 6-(hydroxyamino)uracils 62 with triethyl-orthoformate and nitriles 47 (Z = CN, C02Et) with acetic anhydride at 75 °C for 2-8 min gave pyrano- and pyrido[2,3-d]pyrimidines in excellent yield and also provided a direct route to pyrido[2,3-d]pyrimidine N-oxides (Scheme 27). 

The cycloaddition of alkynes and alkenes to nitrile oxides has been used in the synthesis of functionalised azepine systems <96JHC259>, <96T5739>. The concomitantly formed isoxazole (dihydroisoxazole) ring is cleaved by reduction in the usual way. Other routes to 1-benzazepines include intramolecular amidoalkylation <96SC2241> and intramolecular palladium-catalysed aryl amination and aryl amidation <96T7525>. Spiro-substituted 2-benzazepines have been prepared by phenolic oxidation (Scheme 5) <96JOC5857> and the same method has been applied to the synthesis of dibenzazepines <96CC1481>. 

As mentioned in Sect. 2.2, phosphine oxides are air-stable compounds, making their use in the field of asymmetric catalysis convenient. Moreover, they present electronic properties very different from the corresponding free phosphines and thus may be employed in different types of enantioselective reactions, m-Chloroperbenzoic acid (m-CPBA) has been showed to be a powerful reagent for the stereospecific oxidation of enantiomerically pure P-chirogenic phos-phine-boranes [98], affording R,R)-97 from Ad-BisP 6 (Scheme 18) [99]. The synthesis of R,R)-98 and (S,S)-99, which possess a f-Bu substituent, differs from the precedent in that deboranation precedes oxidation with hydrogen peroxide to yield the corresponding enantiomerically pure diphosphine oxides (Scheme 18) [99]. 

With a-dfsubstituted yUdes the reaction results in the formation of a carbonyl compound and a tertiary phosphine oxide (Scheme 6). 

A highly remarkable and entirely unexpected conversion of aziridine esters 21 into azirine esters 22 was accomplished by subjecting the aziridine to a Swern oxidation (Scheme 11). 

This group showed that isolable silver(I) diaminocarbene complexes can be use in situ instead of free carbenes, to generate the copper carbene complex. The silver salts that precipitates during the formation of the copper complex have not any negative effect on the conversion. This method is advantageous since most of the silver complexes are isolable, air-stable and easily obtained by treatment of the corresponding imidazohnium salt by 0.5 equiv of silver oxide (Scheme 53). The solid structure of 78 was analyzed by X-ray diffraction. 

In addition, also nonheme iron catalysts containing BPMEN 1 and TPA 2 as ligands are known to activate hydrogen peroxide for the epoxidation of olefins (Scheme 1) [20-26]. More recently, especially Que and coworkers were able to improve the catalyst productivity to nearly quantitative conversion of the alkene by using an acetonitrile/acetic acid solution [27-29]. The carboxylic acid is required to increase the efficiency of the reaction and the epoxide/diol product ratio. The competitive dihydroxylation reaction suggested the participation of different active species in these oxidations (Scheme 2). 

Rovis and co-workers have also shown that pre-catalyst 129 is competent with a wide range of Michael acceptors including oc,P-unsaturated aldehydes, amides, nitriles, esters, thioesters, vinylphosphonates and vinylphosphine oxides (Scheme 12.25) [58,60],... 

Figure 5.6 Cost Indices Cl for the biocatalytic (a) and chemical catalytic (b) synthesis of (S)-styrene oxide (Scheme 5.3), using the software EATOS. The bottom figure shows the cost savings achieved by solvent recycling.

Au/C was established to be a good candidate for selective oxidation carried out in liquid phase showing a higher resistance to poisoning with respect to classical Pd-or Pt-based catalysts [40]. The reaction pathway for glycerol oxidation (Scheme 1) is complicated as consecutive or parallel reactions could take place. Moreover, in the presence of a base interconversion between different products through keto-enolic equilibria could be possible. 

Release and Reactivity of tf-o-QMs Although the r 2-o-QM Os complexes 11 are stable when exposed to air or dissolved in water, the quinone methide moiety can be released upon oxidation (Scheme 3.8).16 For example, reaction of the Os-based o-QM 12 with 1.5 equivalents of CAN (ceric ammonium nitrate) in the presence of an excess of 3,4-dihydropyran led to elimination of free o-QM and its immediate trapping as the Diels-Alder product tetrahydropyranochromene, 14. Notably, in the absence of the oxidizing agent, complex 12 is completely unreactive with both electron-rich (dihydropyran) and electron-deficient (A-methylmaleimide) dienes. 

---