Formylation with Dimethylformamide

A further example of electrophilic substitution is the synthesis of pyrazole aldehydes by formylation with dimethylformamide.620,628... 

Isothiazoles are sulfonated readily with oleum97 or sulfur trioxide,98 but formylation with dimethylformamide and phosphorus oxychloride, and acylation under Friedel-Crafts conditions, failed.70 On the basis of spectroscopic studies Anderson76 suggested that a... 

Benzo[l,2-6 4,5-6 ]dithiophene undergoes metallation at the 2-position, allowing formylation with dimethylformamide <83MAC627>, and treatment of a benzo[l,2-6 4,3-6 ]dipyrrole (26a) with LITMP and excess methyl chloroformate afforded a 2-carboxylic ester (26b) <87H(25)70i>. 

The vinamidinium salts needed were prepared from the corresponding arylacetic acids by formylation with dimethylformamide phosphoryl chloride, like (7/)ls ... 

Vilsmeier acylation of pyrroles, formylation with dimethylformamide/phosphoryl chloride in particnlar, is a generally applicable process. The actual electrophilic species is an Al,Al-diaIkyl-chloromethyleneiminium cation (the chloride is available commercially as a solid). " Here again, the presence of a large pyrrole-A-substituent perturbs the intrinsic a-selectivity, formylation of A-tritylpyrrole favonring the P-position by 2.8 1 and trifluoroacetylation of this pyrrole giving only the 3-ketone " the nse of bulky iV-silyl substituents allows P-acylation with the possibility of subsequent removal of the N-snbstituent." The final intermediate in a Vilsmeier reaction is an iminium salt requiring hydrolysis to prodnce the isolated product aldehyde. When a secondary lactam is used, hydrolysis does not take place and a cyclic imine is obtained." ... 

Methoxy-1,2,3,4-tetrahydroisoquinoline has been obtained through lithiation with butyllithium between the methoxyl group and the side-chain in N-pivaloyl 2-(3-methoxyphenyl)ethylamine (X = H), formylation with dimethylformamide to give the formyl compound (X = CHO), followed by cyclisation with 10% hydrochloric acid and finally reduction with sodium borohydride (ref. 150). 

Further substitution of 2,4-disubstituted and most 2,3-disubstituted thiophenes occurs in the free a-position, except when a - -M-substituent in the 3-position strengthens the 4-directing power of a —1—M-sub-stituent in the 2-position. Thus methyl 3-methyl-2-thiophenecar-boxylate is brominated in the 4-position and 3-brorao-2-thiophene-aldehyde is nitrated in the 4-position. Recent investigations on the chloromethylation, sulfonation, mercuration, and nitration of 2,4-di-chlorothiophene, which without proof are assumed to occur in the 5-position serves as examples of the reactivity of a 2,4-disubstituted thiophene. Formylation with iV,A-dimethylformamide and... 

The formyl group is generally introduced via the Vilsmeier reaction by dimethylformamide in the presence of phosphorus oxychloride, by the Sommelet reaction via the corresponding chloromethyl derivative, or by treating the lithio compound with dimethylformamide.87... 

In attempts to formylate the bicyclic compound 5-methyl-9-phenylhy-drazono-6,7,8,9-tetrahydro-4-oxo-4//-pyrido[l,2- z]pyrimidine 3-carboxy-late (129) with dimethylformamide-phosphoroxychloride at 90-100°C, a degenerate ring rearrangement took place, resulting in the formation of 7-(o -chloroethyl)-8-chloro-9-(A,A-dimethylaminomethylene)amino-6,7,8,9-tetrahydro-4-oxo-4H-pyrido[l,2-a]pyrimidine-3-carboxylate (131)... 

The acetylacetonates of chromium, cobalt, and rhodium were found to react with dimethylformamide in the presence of phosphorus oxychloride to yield formyl-substituted chelates (10). This is a well known technique for the introduction of an aldehyde group into reactive aromatic systems. The formylation of the chelate rings is a slow reaction, and by controlling the conditions it is possible to... 

Formylation of organometallics is usually carried out with dimethylformamide (DMF). T. Ross Kelly of Boston College found (7. Org. Chem. 2004,69, 2191) that although o-lithiation of 1 proceeded smoothly, formylation with DMF and with methyl formate failed. The inexpensive Fe(CO), however, worked smoothly. 

Reaction of dyes containing a primary amino group with dimethylformamide and an inorganic acid chloride, e.g., phosphoryl chloride, permits introduction of the formamidinium group (e.g.,57), which is also scissioned off upon heating in the dye bath [154], A similar reaction occurs with the trialkylhydrazinium moiety obtained by reacting formyl-substituted azo dyes with dialkylhydrazines and subsequent quatemization [155],... 

Formylation.2 Dimethylformamide and trifluoromethanesulfonic anhydride form an iminium salt (1) that is more reactive than that formed from dimethylformamide and POCl3, which is generally used for formylation (Vilsmeier reagent). Although the Vilsmeier reagent does not react with naphthalene or phenanthrene, reactions with 1 results in 1-naphthalenacarbaldehyde in 50% yield and in 3-phenanthrenecarbaldehyde in 25% yield. 

The potential of the reverse polarity approach has been spectacularly demonstrated in a plethora of synthetic studies. A representative example can be found in Seebach s preparation of the antibiotic vermiculin. The key step of this synthesis involved the preparation of a polyfunctional intermediate 253 via the sequence shown in Scheme 2.102. The first stage of this sequence couples the formyl anion equivalent 244 with bromoepoxide 254. The primary bromide is more active as an electrophile than epoxide and therefore, under carefully controlled conditions, the product 255 is formed selectively. Under somewhat more stringent conditions the epoxide ring present in the latter adduct reacts as an electrophile with the second acyl anion equivalent 256 to yield adduct 257. In this sequence, 254 was used as an equivalent to the 1,4-doubly charged synthon CH2CH2CH(OH)CH. In the final step of this scheme, carbanion 258 was generated and reacted with dimethylformamide to produce the required product 253. It is remarkable that all of these sequential operations are carried out in one reaction vessel without the isolation of any intermediate products. The overall yield of 253 is rather high (approximately 52%). 

Vilsmeyer-Haack formylation of the tricyclic compounds of types 205 and 333 with dimethylformamide-phosphoryl chloride reagent gave the formylated products 390 (For the structures of 390... 

Alunni, S., Linda, P., Marino, G., Santini, S., Savelli, G. Mechanism of the Viismeier-Haack reaction. II. Kinetic study of the formylation of thiophene derivatives with dimethylformamide and phosphorus oxychloride or carbonyl chloride in 1,2-dichloroethane. J. Chem. Soc.,... 

Formylation, of cyclohexanone with ethyl formate, 39, 27 of indole with dimethylformamide, 39, 31... 

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