Formylation Vilsmeier reagent

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

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. 

Chou had brominated steroid I with l,3-dibromo-5,5-dimethylhydantoin (DB-DMH) to give the bromohydrin, II, which in turn was formylated (Vilsmeier reagent) and treated with base to give epoxide HI ... 

Vilsmeier reagent The reagent obtained from POCI3 mixed with either N,N-dimethyl-formamide or N-methylformanilide. Used for introducing the methanoyl (formyl) (-CHO) group into activated aromatic substrates. 

In the Meth-Cohn quinoline synthesis, the acetanilide becomes a nucleophile and provides the framework of the quinoline (nitrogen and the 2,3-carbons) and the 4-carbon is derived from the Vilsmeier reagent. The reaction mechanism involves the initial conversion of an acylanilide 1 into an a-iminochloride 11 by the action of POCI3. The a-chloroenamine tautomer 12 is subsequently C-formylated by the Vilsmeier reagent 13 derived from POCI3 and DMF. In examples where acetanilides 1 (r = H) are employed, a second C-formylation of 14 occurs to afford 15 subsequent cyclisation and... 

The synthesis reported by Bonjoch and co-workers utilizes a Ni-mediated reductive cyclization of vinyl iodide 82 with concomitant reductive indolenine formation quenching of the presumed intermediate (dehydrotubifoline, 83) with the Vilsmeier reagent affords A-formyl derivative 84 [36b]. Photoisomerization gives norfluorocurarine (22) in low yield. Similarly, Rawal and He produce... 

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>. 

Monor and di-formylation of 2-acetamidothiophene with preformed Vilsmeier reagent has been achieved (Scheme 129) (80S133). Conditions have also been defined for the conversion of acetamidothiophenes directly into thienopyridines (Scheme 130) (78TL2045). 

Amino acid complexes are also nucleophilic towards the Vilsmeier reagent. The cobalt(II) glycine complex (36) gives rise initially to an unusually stable iminium complex, which can be hydrolyzed with concentrated sulfuric acid to the complex of formylglycine (Scheme 13). The formyl group... 

Diethylamino)sulfur trifluoride, 110 Formylation (see also Carbonylation) Vilsmeier reagent, 341 Fragmentation reactions Cerium(IV) ammonium nitrate, 67 Copper(II) acetate-Iron(II) sulfate, 85 Lead tetraacetate, 155 Friedel-Crafts alkylation Aluminum chloride, 15... 

The reduction of azepinone 484 leads to 1,2,3,4-tetrahydroderivative 485, whereas dehydrogenation of 484 by chloroanil results in 1H-naphtho[Mazepine-2-one 486 (76JHC371). The interesting conversion resulting in l//-l-methyl-3-formyl-7-methoxynaphtho[bc]azepine-2-one 490 occurs on interaction of 4-methoxy-8-(N-methyl-N-acetyl)aminonaphthal-dehyde 487 with the Vilsmeier reagent (86ZOR2394). It was assumed that compounds 488 and 489 are intermediates in this reaction. 

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... 

All that remained at this point was the formylation of pyrrole 28 followed by condensation with 5-fluorooxindole (10). While the initial discovery route had accomplished this in two separate steps, the process team developed a one-pot procedure. Thus pyrrole 28 was added to a solution of the Vilsmeier reagent 29 in acetonitrile at room temperature (Scheme 7.5). Following the completion of the formylation reaction,... 

While there are several reports concerning electrophilic substitution on to (5,5)-fused heterocycles, very few of these involve a study with the parent system. The ir-excessive systems (50), (51), (52) and (53) were found to be susceptible to attack by electrophilic reagents at the positions indicated, leading to alkylation, formylation (Vilsmeier-Haack reaction), acylation, tritylation, metalation, tricyanoethylation, halogenation, thiocyanation, nitrosation, nitration and diazo coupling (77HC(30)l). 

Examples of electrophilic attack on N-protected 1,2-dihydropyridines include bromine-mediated addition of Boc-protected-guanidine 534 to dihydropyridine 533 giving, after acid deprotection, f-2-amino-l,3a,S,7a-dihydroimidazo [4,5- ]pyridine 535 <2004OL3933> formation of 5-trichloroacetyl-l,4-dihydropyridines 536 <2003TL4711> and -formylation with the Vilsmeier reagent <20060L179>. -Aminonitriles which are formed by trapping 2,3-dihydropyr-idinium salts with cyanide ion are stable, but easily converted back into 2,3-dihydropyridinium salts with Lewis acids. 

An W-formylated dibenzodiazocine was isolated in some cases in very poor yield <1998J(P1)1257>. Using the same synthetic approach, a series of fused diazocines were obtained. Thus, the action of bis-Vilsmeier reagents derived from W,W -dimethyl-W,W -diformyl-4-phenylenediamine with 4-substituted AUV-dimethylanilines, the diben-zo[ ]benzo[l,2-/4,5-/]bis-l,5-diazocines were obtained <2000S640>. Benzo[2,3]pyrido[6,7-A]-l,5-diazocines were synthesized from a Vilsmeier reagent derived from 4-W-(methylformamido)pyridine reacting with 4-substituted... 

Regioselective formylation was also achieved by treatment of a 3-phenylbenzo[3]furan with AiACdimethylforma-mide and phosphoryl chloride (Vilsmeier reagent) at 0-25 °C to give 2-carbaldehyde derivative in 90% yield (Equation 61). In addition, a variety of interesting 2-acylbenzo[/ ]furan derivatives were described in the same article <2002T5125>. 

The most useful acylation reaction of azaindoles, as with indoles, is 3-formylation. This is carried out conveniently with the Vilsmeier reagent (phosphoryl chloride in dimethylformamide). 

Formylation of Hmoneae. (-i-)-(4R)-Limonene (1) is formylated by the Vilsmeier reagent (2) stereoselectively to give mainly the (E)-of,)3-unsaturated aldehyde 3. The product was used tor the synthesis of (4R),(E)-a-atlantone (5), a sesquiterpene from Cedrus oils. 

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... 

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