Bromination pyridine 1-oxides

Oxidation reactions catalysed by simple vanadium catalysts. Top oxidative bromination of trimethoxybenzene catalysed by dioxovanadium(V) in strongly acidic solution.Centre oxidation of toluene by oxygen, catalysed by vanadate in the presence of a ligand, e.g. ascorbic acid and pyridine. All three isomeric cresols are formed.Bottom the reaction sequence for the formation of hydroxyl radicals, supposedly the actual oxidant modified from the respective scheme provided in ref. 68. 

ACINTENE A (80-56-8) Forms explosive mixture with air (flash point 91°F/33°C). Violent reaction with strong oxidizers, bromine, perchlorates (e.g., nitrosyl perchlorate, etc.), perchromates (pyridine perchromate), sulfuric acid, nitric acid, peroxyacetic acid, peroxyben-zoic acid, and other oxidizing acids. Flow or agitation of substance may generate electrostatic charges due to low conductivity. 

BENZO(b)PYRIDINE (91-22-5) Combustible liquid (flash point 140°-230°F/ 60°-l 10°C). An organic base. Violent reaction with acids, strong oxidizers bromine. 

A -Benzoyloxypyridinium chloride (72), prepared from pyridine oxide and benzoyl chloride, reacts with silver phenylacetylide selectively at position 2 to afford 2-(phenylethynyl)pyridine (73). The bromine atom of the tetrahydro-l,4-oxazin-2-one 74 is replaced by an alkynyl group on treatment with stannanes 75 (R = hexyl or Ph) the products 76 are transformed into ( S)-amino acids 77 by catalytic hydrogenation. ... 

Iodine Acetaldehyde, acetylene, aluminum, ammonia (aqueous or anhydrous), antimony, bromine pentafluoride, carbides, cesium oxide, chlorine, ethanol, fluorine, formamide, lithium, magnesium, phosphorus, pyridine, silver azide, sulfur trioxide... 

Acceptors. Most common acceptor molecules such as tetracyanoethylene or tetracyanoqurno dime thane ate commercially available. However, TCNQ can be synthesized in high yield by a two-step synthesis involving a condensation of malonitrile with 1,4-cyclohexanedione followed by treatment with an oxidizing agent such as bromine or A-bromosuccinamide in pyridine solvent (23) (Fig. 6). 

Bromoacetic acid can be prepared by the bromination of acetic acid in the presence of acetic anhydride and a trace of pyridine (55), by the HeU-VoUiard-Zelinsky bromination cataly2ed by phosphoms, and by direct bromination of acetic acid at high temperatures or with hydrogen chloride as catalyst. Other methods of preparation include treatment of chloroacetic acid with hydrobromic acid at elevated temperatures (56), oxidation of ethylene bromide with Aiming nitric acid, hydrolysis of dibromovinyl ether, and air oxidation of bromoacetylene in ethanol. 

Bromination using NBS has been used to provide acetylpyrazine derivatives from the corresponding ethylpyrazines. Bromination of 2-ethyl-3-methylpyrazine gives 2-bromoethyl-3-methylpyrazine in quantitative yield this may be oxidized using the sodium salt of 2-nitropropane or with pyridine AT-oxide to yield 2-acetyl-3-methylpyrazine in yields of 66 and 25% respectively (Scheme 14). 

As foretold in the introduction, ring formation via attack on a double bond in the endo-trig mode is not well exemplified. The palladium(II) catalyzed oxidative cyclization of o-aminostyrenes to indoles has been described (78JA5800). The treatment of o-methyl-selenocinnamates with bromine in pyridine gives excellent yields of benzoselenophene-2-carboxylates (Scheme 10a) (77BSF157). The base promoted conversion of dienoic thioamides to 2-aminothiophenes is another synthetically useful example of this type (Scheme 10b) (73RTC1331). 

Electrophilic mercuration of isoxazoles parallels that of pyridine and other azole derivatives. The reaction of 3,5-disubstituted isoxazoles with raercury(II) acetate results in a very high yield of 4-acetoxymercury derivatives which can be converted into 4-broraoisoxazoles. Thus, the reaction of 5-phenylisoxazole (64) with mercury(II) acetate gave mercuriacetate (88) (in 90% yield), which after treatment with potassium bromide and bromine gave 4-bromo-5-phenylisoxazole (89) in 65% yield. The unsubstituted isoxazole, however, is oxidized under the same reaction conditions, giving mercury(I) salts. 

Oxidations usually proceed in the dark at or below room temperature in a variety of solvents ranging from aqueous bicarbonate to anhydrous benzene-pyridine. Base is quite commonly used to consume the hydrogen halide produced in the reaction, as this prevents the formation of high concentrations of bromine (or chlorine) by a secondary process. The reaction time varies from a few minutes to 24 hours or more depending on the nature of the reagent and the substrate. Thus one finds that NBS or NBA when used in aqueous acetone or dioxane are very mild, selective reagents. The rate of these oxidations is noticeably enhanced when Fbutyl alcohol is used as a solvent. In general, saturated, primary alcohols are inert and methanol is often used as a solvent. 

The immediate outcome of the Hantzsch synthesis is the dihydropyridine which requires a subsequent oxidation step to generate the pyridine core. Classically, this has been accomplished with nitric acid. Alternative reagents include oxygen, sodium nitrite, ferric nitrate/cupric nitrate, bromine/sodium acetate, chromium trioxide, sulfur, potassium permanganate, chloranil, DDQ, Pd/C and DBU. More recently, ceric ammonium nitrate (CAN) has been found to be an efficient reagent to carry out this transformation. When 100 was treated with 2 equivalents of CAN in aqueous acetone, the reaction to 101 was complete in 10 minutes at room temperature and in excellent yield. 

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