Vilsmeier-Haack-Arnold reaction

The hydrazinoyl-substituted imidazothiadiazole 188 under Vilsmeier-Haack-Arnold reaction conditions gives the tricyclic thiadiazoloimidazopyridazinone 189 <2006SC1837> (Equation 20). 

TL5981>. The proposed mechanism involves the oxidation of the amine to an imine, tautomerization to an enamine, and a sequence of nucleophilic attacks on the pyridazine rings followed by oxidation steps. The oxidant of choice is (bispyridine)silver permanganate <1982TL1847>, which is easily prepared, mild in action, and is soluble in organic media. If R1 = H in the product 77, electrophilic substitution (e.g., bromination, nitration, Mannich, and Vilsmeier-Haack-Arnold reactions) occurs at this position. 

The Vilsmeier (or Vilsmeier-Haack or Vilsmeier-Haack-Arnold) reaction is primarily a mild method for formylating a wide variety of substrates.1 It has limited application to higher acylation and involves the reaction of a Vilsmeier reagent derived from a tertiary amide and an acid chloride (or occasionally a bromide). The most commonly employed amide is jV,N-dimethylformamide (DMF) and the acid chloride is generally phos-phoryl chloride, though phosgene and thionyl chloride are also employed. 

Selinene is another sesquiterpene found in woods. Its behaviour in the Vilsmeier-Haack-Arnold reaction is, like that of the acylation of cedrene using titanic chloride as a catalyst, another interesting and surprising piece of sesquiterpenoid carbocation chemistry. 

The Vilsmeier-Haack-Arnold reaction involves the addition of an imminium ion to an olefin as shown in Figure 6.34. The imminium ion... 

Chlorovinyl aldehydes 16 result from a-methylene ketones by the action of DMF/POCI3 (the Vilsmeier-Haack-Arnold reaction) ... 

New syntheses of ( )-ar-turmerone (79) and ( )-nuciferal (80) have been reported (Schemes 10 and 11 ) whereas Meyers and Smith have used the (+)-oxazoline (81) to good effect in an asymmetrically induced synthesis of (+)-ar-turmerone (82) (Scheme 12). A neat one-pot synthesis of /3-curcumene (83) has been developed which involves only two steps (Scheme 13). In a synthesis of the aromatic analogue, (-)-a-curcumene (84), Kumada et al. have used an asymmetrically induced cross-coupling Grignard reaction in the presence of a nickel complex of (85) to produce (84) in 66% enantiomeric excess (Scheme 14). A Vilsmeier-Haack-Arnold formylation of (-f-)-limonene has been used as... 

Although Vilsmeier and Haack in 1927 were the first who recognized the general applicability of this method, Dimroth and Zoeppritz in 1902 had obtained dihydroxybenzaldehyde from resorcinol, formanilide, and phosphorus oxychloride. The modern mechanistic interpretation of this reaction was advanced by Arnold and Sorm Jutz and Bosshard and Zollinger (, 43 example, when a suitable substrate, such as N,N-dimethylaniline, is treated with the phosphorus oxychloride complex of a N,N-disubstituted formamide, the intermediate iminium chloride... 

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