Halogen-N-oxides

The reactivity of halogens in pyridazine N- oxides towards nucleophilic substitution is in the order 5 > 3 > 6 > 4. This is supported by kinetic studies of the reaction between the corresponding chloropyridazine 1-oxides and piperidine. In general, the chlorine atoms in pyridazine A-oxides undergo replacement with alkoxy, aryloxy, piperidino, hydrazino, azido, hydroxylamino, mercapto, alkylmercapto, methylsulfonyl and other groups. 

IR spectroscopy, 2, 153 cycloaddition reactions, 1, 479 halogenation, 2, 203 hydrogenation, 2, 46 intermolecular cycloadditions, 2, 307 magnetic circular dichroism, 2, 129 N-oxides... 

Nucleophilic halogenations tend to favor the pyridine moiety. The Meisenheimer reaction of thieno[3,2-6]pyridine N-oxide (125) gave only a 24% yield of a 1.4 1 mixture of the 5- and 7-chloro derivatives. Nucleophilic displacement of a 7-nitro group provided a more satisfactory route to the 7-chloro (73%) and 7-bromo (39%) derivatives (85JHC1249). 

Nucleophilic halogenation procedures include Meisenheimer chlorination of the appropriate N-oxides. The 1-methyl 4-oxide of 133 gave a... 

Although the simple mono-(2-,4-,6-, and 7-) and some di-(6,7-, 2,4-) tri-(2,4,6-, 2,4,7-), and tetra-(2,4,6,7-) -chloro derivatives are known, they are often unstable and highly susceptible to nucleophilic attack, and little is known about some of the compounds (64JCS1666 84MI10). No electrophilic halogenations have yet been reported, but there have been a few instances of chlorine introduction by Meisenheimer reaction of pteridine N-oxides (78JOC680 82LA2135). 

On Pd/C, carbon-carbon double bonds and halogens are usually reduced before the N-oxides. The final selectivity in the hydrogenation of N-oxides has been shown to depend on the pH, the catalyst system used, and the functional groups present and their position. PtSx was a superior catalyst with a higher assay and yield in the selective hydrogenation of 6-chloro-2(lH)-hydroxyqui-noxaline-4-oxides (43) (Scheme 4.139).534... 

See other endothermic compounds, n-halogen compounds, oxidants... 

Another synthesis of halopyridines, unique to pyridine and other JV-containing heteroarenes, involves transformation of pyridine N-oxide into the corresponding pyridone followed by halogenation. In one case, treatment of 3-chloro-2,4 -bipyridine-l -oxide (8) with acetic anhydride produced the pyridone, which was then converted to dichloride 9 with POCls/DMF [7]. 

Instruments are available for determination of N alone, CHN, CNS and CHNS. N determination in one of the CHN models involves removal of all nonnitrogenous combustion products, including halogens and various oxides, reduction of N oxides to N2, removal of excess oxygen, dilution with helium and measurement with a thermal conductivity... 

There are several examples of the 1,2-elimination of hydrogen chloride from 9-(2-chloroethyl)carbazoles, using potassium hydroxide in ethanol, generating the 9-vinylcarbazoles. 3-Dimethylamino-9-(2-hydroxyethyl) carbazole comparably lost water on base treatment. Dimethylamine displacement of halogen, then amine N-oxide formation and elimination was utilized to produce 9-alkenylcarbazoles with four, five, and six carbon atoms from the corresponding cu-haloalkyl carbazoles. ... 

Methylisothiazolo[5,4- ]pyridin-3-(2//)-one-l-oxide 103 was quantitatively obtained by treating 104 with chlorine in aqueous acetic acid (Equation 13). The oxidation of 104 with Oxone at 60 °C in aqueous methanol gave 2-methylisothiazolo[5,4- ]pyndin-3-(2//)-one 1,1-dioxide 105 in a single step (Equation 14). No C-halogenation or N-oxidation products were detected under these reaction conditions <1996T8947>. 

Isocyanides have been oxidized to isocyanates with HgO and with Oj, as well as with a halogen and dimethyl sulfoxide (or pyridine N-oxide).428 In the latter case the oxidizing agent is the halogen, which converts the isocyanide to R—N=CCI which is hydrolyzed to the isocyanate.429 Cyanide ion has been oxidized to cyanate ion with many oxidizing agents. 

The only alkyl group reported as reductively removed is the di-phenylmethyl substituent from N3 in compound 165.153 Deoxygenation of N-oxides can be done thermally (heating in toluene with oxygen transfer to solvent) for compounds of type 166,44 or more commonly by use of phosphorus derivatives, as described for compounds 32, 33,45 166,44 and 167.61 Halogens can be reductively removed from [l,2,3]triazolo-[4,5-6]pyridines 160,146 168,220 and 169,142 and from pentachloro derivative 164, giving dichloro compound 170.208 Removal of thiol groups by reduction... 

Amino groups in pyridazine N- oxides can be diazotized and the diazonium group further replaced by halogens, hydroxy group or hydrogen. So, 3-, 4-, 5- and 6-bromopyridazine 1-oxides can be prepared from the corresponding amino N- oxides. 

In the case of substituted phenazine N-oxides some activation of substituents towards nucleophilic substitution is observed. 1-Chlorophenazine is usually very resistant to nucleophilic displacements, but the 2-isomer is more reactive and the halogen may be displaced with a number of nucleophiles. 1-Chlorophenazine 5-oxide (56), however, is comparable in its reactivity with 2-chlorophenazine and the chlorine atom is readily displaced in nucleophilic substitution reactions. 2-Chlorophenazine 5,10-dioxide (57) and 2-chlorophenazine 5-oxide both show enhanced reactivity relative to 2-chlorophenazine itself. On the basis of these observations, similar activation of 5- or 6-haloquinoxaline iV-oxides should be observed but little information is available at the present time. 

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