Ketones Vilsmeier reagent

Amino groups react very easily with aldehydes or ketones, and with aldehydes in the presence of amines, they can be acylated by the usual acylating agents, and they react with amidacetals, Vilsmeier reagents and nitroso compounds (Scheme 12). As mentioned earlier, alkylation leads mainly to AT(2)-alkylated products. The hydrazino group reacts in the same way as the amino group with aldehydes or ketones, with acyl chlorides or carboxylic anhydrides, with sulfonyl chlorides, ortho esters, carbon disulfide and with nitrous acid. The last three reactions have mainly been used for the synthesis of condensed 1,2,4-triazines. 

The synthesis of polymethines with dimethylene bridges starts with alicydic ketones (31), ketals (32), and enamines (X = NR2), or enol ethers (X = OR) (33). They possess two activated centers, methine or methylene groups, which react with Vilsmeiers reagent to produce the corresponding dyes. 

Keywords methyl phenyl ketone, 2-phenyl indole, formylation, Vilsmeier reagent, silica gel, microwave irradiation... 

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

Most of these reactions need no comment beyond the fact that the products are mainly 6/9-substituted A -3-ketones. The Vilsmeier reagent is unusual in leading to a product which is still an enol ether [212], probably as a result of the stabilisa-... 

Vilsmeier reagent (Me2N=CHCl OPOCI2), which converts many ketones into vinylic chlorides, may react further to give a -formyl derivatives. The 3,5-dien-7-one (253) affords the 7-chloro-2-formyl-2,4,6-triene (254). A 4,6-dien-3-one gave... 

Recent literature refers to the stereoselective and asymmetric epoxidation of allylic alcohols with organoaluminium peroxides. PhaSiOOH epoxidizes olefins with a stereoselectivity similar to that with peracid. Reports have been made of a-substituted hydroperoxides (acids, esters, ketones, amides, and nitriles) as effective epoxidizing reagents and the application of hexachloroacetone, tetrachloracetone, and hexafluoroacetone hydroperoxide, as well as the HaOa-Vilsmeier reagent system. ... 

Vanadium pentoxide, 39, 1057 Vanillic acid, 898, 937,1012, 1013 Vanillin, 30, 31, 479, 864, 937, 1012, 1031, 1288-1289 o-Vanlllin, 31,468 Vegetable ivory, 838 Veratraldehyde, 468,1025 Veratramine derivative, 780 Veratric acid, 66 Veratric amide, 469 Veratrole, 127, 495, 898, 1018,1019 Veratronilrile, 479 Vernamycin Ba, 181 Vetivazulene, 368-369 Vilsmeier reagent, see Dimethylformamide-Phosphotyl chloride Vinca alkaloids, 648 Vincadiffbrmine, 648-649 Vinyl acetate, 492, 648,1020,1271 Vinylacetylene, 375, 698 Vinylamines, 41 Vinyl-n-butyl ether, 172 Vinyi d-carbomethoxyethyl ketone, 682, 1271-1272... 

The acetal (144) has been converted by the Vilsmeier reagent into the methoxy-enal (145), from which a variety of heterocyclic compounds has been obtained. The enal will condense with reactive methylene compounds, and reacts with lithium alkyls to give, after hydrolysis, ajS-unsaturated ketones of general structure (146) these are reducible to saturated ketones, which would otherwise be available only by Diels-Alder addition of dienophiles that are difficult to obtain, to thebaine. ... 

Many examples use steroids as substrates. The simple 3 ketal 72 shows the generally preferred substitution in position 2 (Eq. 65). The diene 73 illustrates the successful use of a Vilsmeier reagent in the presence of a second reactive group (a methyl ketone Eq. 66). Steroid 74 with an exocyclic ketal shows that cyclization can occur to a suitable adjacent substituent (Eq. 67). ... 

Vilsmeier reactions on 1,3-diketones, 1,4-diketones, and conjugated enones give cyclic products as shown by the reactions of compounds 86 (Eq. 81), 87 (Eq. 82), and 88 (Eq. 83). The reaction of the Vilsmeier reagent with a,jS-epoxy ketones also gives benzaldehydes or 1,3-phthalaldehydes (Eq. 83a) ... 

Alicyclic ketones, even cyclobutanone, react well with Vilsmeier reagents without the ambiguity of stereochemistry observed in acyclic examples. Thus cyclohexanone 101 gives a chloroenal as does A-benzoylpiperidone (102 Eq. 94). " The products may be converted into the synthetically useful ketal... 

Chromones. 3-Substituted chromones, including isoflavones (3-arylchro-niones), can be prepared in fair to excellent yields by treatment of 2-hydroxy-phcnyl alkyl (arylalkyl) ketones (I) with BF3 etherate (exothermic reaction) in DMF. Metlianesulfonyl chloride in DMF (Vilsmeier reagent) is then added at 52 and (he reaction is warmed on a steam bath (90 minutes). Chromones (2) arc obtained in 65 96% yield. The function of BF , etherate is to deactivate the hydroxylalcd aromatic ring hy complex formation and thus prevent ring lormylalion. 

The formylation of polyene aldehydes and o,jS-unsubstituted ketones with the Vilsmeier reagent (DMF-POCI3) has been reported recently. For example, reaction of the ketones XXIV with the Vilsmeier reagent produces the iminium salts XXV, which are hydrolyzed to the aldehydes XXVI. The latter compounds form the conjugated ene-yne derivatives XXVII upon addition of their dioxane solution to dilute sodium hydroxide at 80-90°C... 

However, the reactions of most non-aromatic n nucleophiles with Vilsmeier reagents yield more complicated products." The reaction of the following ketone, via its enol tautomer, is illustrative. ... 

The Bishler-Napieralski reaction, described above, is a named reaction in which Vilsmeier formylation results in a molecule that can participate in a subsequent cyclization reaction, resulting in a net annulation. There are numerous other examples of similar tandem sequences, most of which are not named reactions, and they generally give only modest yields. For instance, when ketone 25 is treated with a Vilsmeier reagent, isoflavone 26 is produced in nearly quantitative yield. ... 

The stabilized phosphonium ylide (601) reacts with aromatic aldehydes to give N-phenacylpyrazoles (602) in good yields (73CC7). Ketone semicarbazones and ketazines react with two moles of phosphorus oxychloride-DMF, the Vilsmeier-Haack reagent, with the formation of 4-formylpyrazoles (603 R = H or PhC=CH2) (70JHC25, 70TL4215). 

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),... 

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. 

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