Vilsmeier reagent reaction with

Vilsmeier reagent, reaction with ketones to form 0-chloro- ,3-unsaturated aldehydes, 46,19... 

Reaction with a purine nitriie. The Vilsmeier reagent reacts with (I) to give a hygroscopic gum considered to be a ketenimine (2), which reacts with water or... 

Aromatic and heterocycHc compounds are formylated by reaction with dialkyl- or alkylarylformamides in the presence of phosphoms oxychloride or phosgene (Vilsmeier aldehyde synthesis) (125). The Vilsmeier reaction is a Friedel-Crafts type formylation (126), since the intermediate cation formed by the interaction of phosphoms oxychloride with formamide is a typical electrophilic reagent. Ionic addition compounds of formamide with phosgene or phosphoms oxychloride are also known (127). 

Typically, an acetanilide (1 mol. equiv.) was treated with the Vilsmeier reagent generated from POCI3 (7 mol. equiv.) and V,V-dimethylformamide (DMF, 2.5 mol. equiv.) at 75 °C for 4 - 20 h. The reaction products were readily obtained by filtration after pouring the reaction mixture onto ice-water minor reaction products were isolated after basification of the filtrate. A variety of acetanilides were studied under these optimised reaction conditions and some significant observations were noted. Activated acetanilides 3 [e.g. R = 4-Me (70%), 4-OMe (56%)] reacted faster and in better yield to give quinolines 4 than other strongly deactivated systems 3 [e.g. R = 4-Br (23%), 4-Cl (2%), 4-NO2 (0%)] — in these cases, formamidines 5 and acrylamides 6 were the major reaction products. 

Pyrrolo[ 1,2-b [l, 2,4[triazinium salt 30 was obtained (90CB2039) by the reaction of hydrazone 29 with the Vilsmeier reagent prepared from DMF and oxalylchloride (Scheme 9). 

The reaction with disubstituted formamides and phosphorus oxychloride, called the Vilsmeier or the Vilsmeier-Haack reaction,is the most common method for the formylation of aromatic rings. However, it is applicable only to active substrates, such as amines and phenols. An intramolecular version is also known.Aromatic hydrocarbons and heterocycles can also be formylated, but only if they are much more active than benzene (e.g., azulenes, ferrocenes). Though A-phenyl-A-methyl-formamide is a common reagent, other arylalkyl amides and dialkyl amides are also used. Phosgene (COCI2) has been used in place of POCI3. The reaction has also been carried out with other amides to give ketones (actually an example of 11-14),... 

Formation of a pyridine ring onto bis-heterocycles is another route to these tricyclic systems. Reaction of 4-amino-2-morpholino-5-(2-morpholinothiazoM-yl)thiazolc 154 with the Vilsmeier reagent proceeds by direct cyclization to the bis-thiazolylpyridine 155 (Equation 36) <1997JHC1291>. 

The reaction of 3-isonitrosopyrazolo[5,l-6]quinazolin-2,9-dione 453 with the Vilsmeier reagent gave the expected o-cyanoamidine derivative, which was cyclized [77IJC(B)335] by hydroxylamine to [l,2,4]triazino[6,l-b]quinazolin-10-one 454. 

The reaction of compounds 161 with the Vilsmeier reagent affords 5-formyl-6-substituted imidazo[2,l- ][l,3,4]thia-diazole-2-iV-(dimethylaminomethino)sulfonamides 168 (Equation 7) <1999AF858>. 

The Vilsmeier-Haack reagent, a chloroiminium salt, is a weak electrophile. Therefore, the Vilsmeier-Haack reaction works better with electron-rich carbocycles and heterocycles. 

Wuts and co-workers recently reported that the Vilsmeier reagent is superior to thionyl chloride for the cyclodehydration of primary and secondary p-hydroxy amides to prepare oxazolines, in particular, for oxazoline 18b, which is used in Taxol synthesis (Scheme 8.10). Some other examples are shown in Table 8.5 (Fig. 8.3). As expected, inversion of configuration at the alcohol bearing carbon atom is observed. Of the examples examined, serine afforded low yields due to the formation of dehydroalanine. The reaction is conveniently carried out in pyridine at room temperature. p-Chloro amides are also formed, which can be converted to the oxazoline with DBU, generally using the same mixture without isolation. The... 

As Scheme 23 illustrates, DMF reacts with POCI3 to form Vilsmeier reagent 158. Aryl-Pd-I species 159, generated by the oxidative addition of iodotoluene 160 to Pd(0) species, reacts with the reagent 158 to yield chloroiminium ion 162 via an adduct 161 through a hetero-Heck-type reaction mechanism, and liberates H-Pd-I species. Finally, the hydrolysis of chloroiminium ion 162 gives amide 163. 

The reaction of 2,3-dihydro-1//- pyrrolizin-1 -one with phosphorus oxychloride and DMF at -50 °C results in the formation of (77) but, at 0°C with an excess of the Vilsmeier reagent, further reaction yields (78) (79CB2465). In contrast, the benzopyrrolizinone (79) reacts only with difficulty under similar reaction conditions to give the monoformyl derivative... 

Benzofuran-3(2/f)-ones (396) exist in the keto form but undergo ready enolization. Acetylation with acetic anhydride and sodium acetate affords 3-acetoxybenzo[6]furans, but reaction under acidic conditions usually supplies these products admixed with 3-acetoxy-2-acetylbenzo[6]furans. Alkylation usually furnishes a mixture of O- and C-alkylated products. 3-Acetoxy-6-methoxy-4-methylbenzo[6]furan, on Vilsmeier reaction, supplies the 3-chlorobenzo[6]furan-2-carbaldehyde, the product expected from an enolizable ketone (72AJC545). Benzofuran-3(2//)-ones react normally with carbonyl reagents. Grignard reagents react in the expected way and dehydration of the intermediate affords a 3-substituted benzo[6]furan. The methylene group is reactive so that self condensation, condensation with aldehydes and ketones and reaction with Michael acceptors all occur readily. 

Formation of l,2,4-triazolo[l,5-c]pyrimidine-5(6//)-thiones or their 5(6//)-ones by the reaction of l,4,6-triaminopyrimidine-2(l//)-thiones (468) with the Vilsmeier reagent has been found to be dependent on the temperature. Thus, treatment of 468 with phosphoryl chloride and DMF at 0-5°C afforded mainly the thiadiazolopyrimidinium chloride 470 in addition to the thione 471, but at 25°C a mixture of 471 and 7-formamido-l,2,... 

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