Phosphoryl chloride Vilsmeier reagents from

Bischler-Napieralski isoquinoline synth., 293 Phosphoryl chloride (phosphorus oxychloride)t Vilsmeier reagents from, 16,. 255, 293 Photochemical reactions ... 

The reactions of isoxazolin-5-ones (1379) with 1 mol of phosphoryl chloride and DMF in boiling chloroform for 1.5 hr afforded 1,3-oxazin-6-ones (1381) in 69-74% yields via aminomethylenemalonate derivatives (1380) (87JOC3426). If 2 mols of Vilsmeier-Haack reagent were used in boiling carbon tetrachloride for 2 hr, then 1381 (R = H) and the amino-methylenemalonamate derivative (1382) were obtained in 8% and 76% yields, respectively, from 1379 (R = H). 

The resulting enamine 25 then reacts with the Vilsmeier reagent 27, which results from DMF and phosphoryl chloride by way of intermediate 26 Elimination of hydrogen chloride leads to compound 28. Ring closure presumably occurs via intermediate 29. Rearomati/.ation with elimination of dimethylamine produces the desired quinoline 9. 

Vilsmeier formylation has attracted much attention as a route to cyclazines (see Section III,B,6). Jessep and Leaver have obtained the Vilsmeier salt 263 from 1 by using dimethylformamide and phosphoryl chloride at — 65°C, but the formylpyrrolizine was very unstable, and a second Vilsmeier reaction has not been achieved.128 The salt 263 could be converted to the 3,5-bisaldehyde equivalent 264a by treatment with dimethylthioformamide and acetic anhydride. Flitsch et al. prepared l-chloro-3H-pyrrolizine and treated it in situ at — 60°C with the Vilsmeier reagent to obtain the chloro derivative 259 of compound 263. 7 They also obtained the bis(dimethylaminomethylene) derivative 264b and, at room temperature, the tris(dimethylaminomethylene) derivative 265, which was hydrolyzed to give the dialdehyde 266. Reactions... 

Note The most common Vilsmeier reagent, chloromethylenedimethylammo-nium chloride (C1CH=N+Me2 Cl-), may be generated in situ from dimethyl-formamide (DMF) with an acid chloride like phosphoryl, thionyl, oxalyl chloride, and so on. 

Other cyclizing agents include the Vilsmeier-Haack reagent prepared from DMF and phosphoryl chloride (27CB119) which permits the formylation and cyclization of 4,5-diaminopyrimidines to be carried out at low temperatures (6UCS5048) and is especially valuable for the preparation of chloropurines from chloropyrimidines. A modified Vilsmeier-Haack procedure which involves cyclization of an intermediate azomethine (253) at low temperatures in situ has also been applied to chloropurine synthesis (6UCS5048). 

The Vilsmeier reagent (VR) derived from dimethylformamide and phosphoryl chloride has been convincingly shown to have structure l2 despite much debate. Erroneous structures are still reported.3... 

The Vilsmeier-Haack reagent, prepared from dimethylformamide and phosphoryl chloride, converts 2-amino-5-(4-pyridyl)nicotinonitrile 1-oxide (45) into 7-chloro-6-(4-pyridyl)pyrido-[2,3-c/]pyrimidin-4(3f/)-one (46),72 this reaction also being an example of the conversion of an A-oxide into an st-chloro group. 

The Vilsmeier complex prepared from dimethylformamide and phosphoryl chloride has been used as a C, unit to cyclize 5-acetyl-6-amino-l,3-dimethyluracil. Subsequently, the resulting 5-hydroxy group is converted into achloro substituent by the same reagent. Thus, after 2 hours at 60°C, 5-chloro-l,3-dimethylpyrido[2,3-c/]pyrimidine-2,4(l//,3A)-dione (26) is obtained.183... 

The reaction of 4-methyl-2-phenylpyrimidine-5-carboxylic acid with the reagent prepared from diethylformamide and phosphoryl chloride yields 6-ethyl-2-phenyl-5-oxo-5,6-dihydropyri-do[4,3-c/]pyrimidine-8-carbaldehyde (8), the aldehyde function in the 8-position resulting from a Vilsmeier formylation.520... 

The 8-methylene carbon atom in 5,6,7,8-tetrahydroquinazoline was activated by the pyrimidine ring, and reacted with formamide and phosphoryl chloride (a Vilsmeier reagent) to form 8-formamidomethylene-5,6,7,8-tetra-hydroquinazoline.197 The latter was also obtained as a by-product in the synthesis of 5,6,7,8-tetrahydroquinazoline from cyclohexanone and trisform-amidomethane.1982-Phenyl-5,6,7,8-tetrahydroquinazoline-4(3//)-thione was synthesized from 1-morpholinocyclohex-l-ene and benzoylisothiocyanate. The thione group underwent the usual metathesis reactions.199 2-Methyl-5,6,7,8-tetrahydroquinazoline-4(3//)-thione was oxidized with potassium permanganate to 2-methyl-4-sulfo-5,6,7,8-tetrahydroquinazoline, which provided 2-methyl-5,6,7,8-tetrahydroquinazolin-4(3//)-one on hydrolysis.145... 

The Vilsmeier-Haack reaction leads to the formation of aromatic aldehydes starting from reactive aromatic compounds. The usual reagent combination is phosphoryl chloride or phosgene together with V-methylformanilide (MFA) or VA -dimethyl-formamide (DMF) [139,140]. First, a V,V-dimethyliminium salt, e.g. 63, is formed which, after basic hydrolysis, gives carbaldehyde. 

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