Pyridine, 4-methoxy-1-oxide

Pyridine 1-oxide, 4-methoxy-2,6-dimethyI-kinetie data, 2, 197 (73JCS(P2)1065)... 

Substituted pyrimidine N-oxides such as 891 are converted analogously into their corresponding 4-substituted 2-cyano pyrimidines 892 and 4-substituted 6-cya-no pyrimidines 893 [18]. Likewise 2,4-substituted pyrimidine N-oxides 894 afford the 2,4-substituted 6-cyano pyrimidines 895 whereas the 2,6-dimethylpyrimidine-N-oxide 896 gives the 2,6-dimethyl-4-cyanopyrimidine 897 [18, 19] (Scheme 7.6). The 4,5-disubstituted pyridine N-oxides 898 are converted into 2-cyano-4,5-disubsti-tuted pyrimidines 899 and 4,5-disubstituted-6-cyano pyrimidines 900 [19] (Scheme 7.6). Whereas with most of the 4,5-substituents in 898 the 6-cyano pyrimidines 900 are formed nearly exclusively, combination of a 4-methoxy substituent with a 5-methoxy, 5-phenyl, 5-methyl, or 5-halo substituent gives rise to the exclusive formation of the 2-cyanopyrimidines 899 [19] (Scheme 7.6). The chemistry of pyrimidine N-oxides has been reviewed [20]. In the pyrazine series, 3-aminopyrazine N-ox-ide 901 affords, with TCS 14, NaCN, and triethylamine in DMF, 3-amino-2-cyano-pyrazine 902 in 80% yield and 5% amidine 903 [21, 22] which is apparently formed by reaction of the amino group in 902 with DMF in the presence of TCS 14 [23] (Scheme 7.7) (cf. also Section 4.2.2). Other 3-substituted pyrazine N-oxides react with 18 under a variety of conditions, e.g. in the presence of ZnBr2 [22]. 

Pyridine 1-oxide is nitrated (H2SO4/HN03, 100°C) to give the 4-nitro derivative in good yield. Substituted pyridine oxides such as the 2- and 3-methyl, -halo and -methoxy derivatives also give... 

Omeprazole is obtained [15] by the reaction of acetyl ethyl propionate 1 with ammonia to give ethyl -3-amino-2,3-dimethyl acrylate 2. Compound 2 was converted to to 2,4-dihydroxy-3,5,6-trimethyl pyridine 3 by treatment with methyl diethylmalonate. Treatment of compound 3 with phosphorous oxychloride produced 2,4-dichloro-3,5/6-trimethyl pyridine 4. 4-Chloro-3/5,6-trimethyl pyridine 5 was obtained by treatment of compound 4 with hydrogen. On treatment of compound 5 with hydrogen peroxide and acetic acid, 4-chloro-3,5,6-trimethyl-pyridine-N-oxide 6 was produced. Treatment of compound 6 with acetic anhydride gave 4-chloro-2-hydroxymethyl-3,5-dimethyl pyridine 7 which was converted to 2-hydroxymethyl-3,5-dimethyl-4-methoxypyridine 8 by treatment with sodium methoxide. Compound 8 was treated with thionyl chloride to produce 2-chloromethyl-3,5-dimethyl-4-methoxypyridinc 9. Compound 9 interacts with 5-methoxy-2-mercaptobenzimidazole to give 5-methoxy 2-[((4-methoxy-3,5-dimethyl-2-pyridinyl)methyl)thio]-lH-bcnzimidazole 10 which is oxidized to omeprazole 11. 

E. 4-Methoxy-2-[[(i S)-(5-methoxy-lid-benzimidazole-2-yl)sulfinyl] methyl]-3,5-dimethyl-pyridine-l-oxide... 

MOPO 4-methoxy, pyridine-N-oxide HDBM dibenzoyl methane... 

Two other nucleophilic substitution reactions of pyridine iV-oxides deserve mention and further study to determine the effects of substituents. Pyridine N-oxide, benzoyl chloride, and the piperidine enamine of cyclohexanone give a good yield of 2-(2 -pyridyl)cyclo-hexanone (155) (63%).360 When W-methoxy-4-picolinium methyl... 

Pyridin-1-oxid 6-Phenyl-3,4,5,6-tetrahydro- X/4, 323 3H-Pyrrol 3-Methoxy-2-phenyl-4,5-dihydro- E6a, 626 [R2N —... 

Alkylpyrazines with other substituents have been oxidized to carboxylic acids as follows 2-acetamido-6-methylpyrazine was oxidized in aqueous magnesium sulfate with potassium permanganate to 2-acetamido-6aqueous potassium permanganate at room temperature to 2-carboxy-3-chloropyrazine, which was also obtained by oxidation of 2-chloro-3-methylpyrazine with selenium dioxide in boiling aqueous pyridine (947). Oxidations of 2-methoxy-3-methyl-... 

On treatment of both quinoline and pyridine /V-oxides with bromine and thallium(iil) acetate, y-bromo-derivatives are formed pyridine JV-oxides are the less reactive substrates/ The reaction of 8-methoxyquinoline iV-oxide with acetic anhydride and methanol yields 84% of 2,8-dimethoxyquinoline. Similarly, the reaction of the 6-methoxy-iV-oxide and ethanol and acetic anhydride gives 2-ethoxy-6-methoxyquinoline, but, under the same conditions, the 7-methoxy-N-oxide is unchanged/ The Reissert compounds (149) derived from substituted quinolines, on treatment with thallium(lll) nitrate and trimethyl orthoformate, undergo either smooth ring-contraction or oxidative debenzoyl-ation, depending on the substitution pattern in the aromatic ring (Scheme 61)/ ... 

It was noted that the 2-(2-hydroxyphenyl)pyridine N-oxide and its methyl ether, like orellanine itself and its tetramethyl ethers (295,296,298,314), are more prone to undergo loss not only of the oxygen atom but also of the hydroxyl or methoxy group, respectively, at the begining of MS fragmentation with the formation of an isoxazolinium-type cation. This would confirm the assumption (315) that the deoxidation mechanism also involves the process shown for the model compound in Scheme 55. 

Wrt methoxy pyridine N-oxides [Cu(4-CH30 CsH NOJCClOJj 398 1.86 Farad square planar coordination 67W10... 

Amino-2-methoxypyridine is acetylated to give the acetyl derivative that, when treated with perbenzoic acid in chloroform, gives 4-amino-2-methoxy-pyridine-1-oxide. Similarly, 4-amino-3-chloropyridine-l-oxide is obtained from 4-amino-2-chloropyridine. 

Synthesis of different substituted dienal-oximes and pyrazole Addition of an activating group (e.g., chlorine, methoxy, etc.) at the 2 position of pyridine A-oxide 70 gives a diverse set of funetionalized dienal-oximes 71, which were used as starting materials in the synthesis of eonjugated nitriles, aliphatie primary and secondary amines, eiraminones and the substituted pyrazole 73 [86-88] (Scheme 12.19). 

Under the protection of nitrogen, compound 3.63 (40 mg, 0.089 mmol) was dissolved in toluene (3 mL) at room temperature, and then, 4-methoxy-pyridine N-oxide (100 mg, 0.80 mmol) and sodium bicarbonate (89 mg, 0.89 mmol) were added. The reaction was kept refluxed at 125 °C for 8 h. After filtration, the solvent was removed by rotary evaporator, and the resulting cmde product was separated by flash column chromatography (PE/EA = 2 1) to give 27 mg colorless liquid (Rf = 0.40, PE/EA = 2 1), yield 80 %. 

Activation in terms of Ea is in the order 4- > 2- > 3-position for the methoxy-dechlorination of chloro-pyridines, -p3rridine A-oxides, and -pyridine quaternary salts (Table II). In methoxylation and piperidination of the 2-, 3- and 4-chloro derivatives of pyridine, nitrobenzene (Table VIII), pyridine A-oxide, and 1-methylpyridinium cation, the activation in terms of is in the order benzene C—<... 

With methoxy and ethoxy pyridine N-oxides K 10 emu/mole K 10 emu/mole ... 

---