Aldehydes halogen-atom substituted

Nucleophilic substitution of the halogen atom of halogenomethylisoxazoles proceeds readily this reaction does not differ essentially from that of benzyl halides. One should note the successful hydrolysis of 4-chloromethyl- and 4-(chlorobenzyl)-isoxazoles by freshly precipitated lead oxide, a reagent seldom used in organic chemistry. Other halides, ethers, and esters of the isoxazole series have been obtained from 3- and 4-halogenomethylisoxazoles, and 3-chloro-methylisoxazole has been reported in the Arbuzov rearrangement. Panizzi has used dichloromethylisoxazole derivatives to synthesize isoxazole-3- and isoxazole-5-aldehydes/ ... 

A dihallde will not do as it would be unreactive towards substitution and we already have three halogen atoms in (3). The answer Is to use the aldehyde (4) -chloral - in acid solution. One addition gives the alcohol (5) which dehydrates and reacts again via a carbonium ion. In practice (5) need not be Isolated. 

Acyl-substituted imidazoles have distinctive UV and IR spectra, and can exist as hydrates in solution, e.g. imidazole-2-carbaldehyde. The aldehyde group is sufficiently electron withdrawing to assist nucleophilic displacement of an adjacent halogen atom. The normal aldehyde derivatives such as oximes, acetals and hydrazones can be formed, and the kinetics of oxime formation with the 4-carbaldehyde have been studied. The tautomeric ratio (zwitterion uncharged aldehyde form) of 1-substituted imidazole- and benzimidazole-2-aldoximes rises in parallel with an increase in basicity of the parent molecule (73CHE1074). These compounds have been shown by NMR studies to adopt the syn configuration. With hydrazine hydrate, imidazole-4,5-dicarbaldehydes give imidazo[4,5-d]pyridazines (208 Scheme 110). 

The Hantzsch synthesis involves three intermediate steps. In the first, the halogen atom of the or-halo aldehyde or a-halo ketone is nucleophilically substituted. The resulting iS-alkyliminium salt 2 undergoes a proton transfer (2 -> 3) cyclization produces a salt of a 4-hydroxy-4,5-dihydrothiazole 4 which is converted into a 2,5-disubstituted thiazole 1 in protic solvents by an acid-catalysed elimination of water. 

Substitution of the halogen atom of Nbd-Cl by a hydrazine residue yields a reagent analogous to Dns-H [404] which is also suited to the determination of aldehydes and ketones. The hydrazones are formed in 99% yield. 

Literature reveals that in the oxidative cyclization of aldeltyde and o-phenylene-diamine, the formation of the required 2-aiyl-l/f-benzimidazole is accompanied by the occurrence of 1-benzylated 2-aryl-1/f-benzimidazoles as side products [46], and sometimes these disubstituted derivatives have been isolated as the main product [47, 48]. The present protocol gives 2-aryl-1/7-benzimidazole selectively. Further, we extended our studies on oxidative reactions of aldehydes with o-aminothiophe-nol. Although thiols are good nucleophiles and SET agents [49], in present studies, no substitution of the halogen atom or the nitro group, dealkylation/debenzoy lation, took place as reported earlier [50-52]. Fmiher, the dithioacetal formation is a common reaction of aldehydes with thiols [53] no competitive dithioacetal formation was observed imder the present conditions. Doping of Mn promotes the activity and... 

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