By the Vilsmeier Formylation

The variation of reactivity towards electrophiles follows the same pattern for metallocenes and phosphametallocenes. Thus, phosphacymantrenes are much less reactive than phosphaferrocenes. A good illustration is given by the Vilsmeier formylation. Both mono- and diphosphaferrocenes are formylated in this way whereas phosphacymantrene does not react ... 

The cyanovinylene moiety is constructed by the Knoevenagel condensation of a suitable aldehyde with an aryl acetonitrile derivative using potassium r-butoxide. EDOT carboxaldehyde was prepared by the Vilsmeier formylation of EDOT with POC1.J and DMF while EDOT acetonitrile was prepared by the Ni(acac)2 catalyzed coupling of EDOT-ZnCl with bromoacetonitrile as shown below 8). 

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... 

Of great importance for porphyrin chemistry is the introduction of carbon substituents by Vilsmeier formylation100 or Friedel-Crafts acylation.100 The introduced substituents allow further carbon-chain elongations and other transformations so that interesting porphyrin derivatives can be synthesized. The Vilsmeier formylation of copper octaethylporphyrin (5) takes place at themethine position. The copper can then be easily removed by treatment with acid.105... 

The Vilsmeier formylation of copper deuteroporphyrin dimethyl ester (6) in which unsubstituted /3-positions are present yields a complex mixture of mono- and disubstituted formylation products which can be partially separated by chromatography on neutral alumina.106... 

In structural and synthetic chemistry, we also find instances of reconsideration 3-(3-methoxyphenoxy)-2-butanone gives by ringclosing dehydration a mixture of 2,3-dimethyl-4-methoxybenzofuran and 2,3-dimethyl-6-methoxybenzofuran,101 not just the 6-derivative.102 2-Ethyl-7-methoxybenzofuran is not formylated in position 3 by the Vilsmeier-Haack reaction, but in position 4.10,103... 

Metalation of thieno[ 3,4-6]thiophene (3) with one equivalent of n-butyllithium at —20° followed by dimethylformamide produced a mixture of 4-formyl (194) and 6-formylthieno[3,4-6]thiophene (195) in a 1 4 ratio, in contrast to the 7 3 ratio obtained by the Vilsmeier formyla-tion of thienothiophene 3.167... 

In the Vilsmeier formylation of iV-( 3-hydroxyethyl)anilines the hydroxyl group is simultaneously replaced by chlorine [60], The resulting aldehydes condense with l,3,3-trimethyl-2-methyleneindoline to form very brilliant dyes [61], With 4-(W-methyl-iV- 3-chloroethylamino)benzaldehyde a commercial dye is obtained. A methyl group in the 2-position to the methine chain produces a bluish-red color (27). 

The combination of tertiary amides, such as dimethylformamide, and phosphoryl chloride generates reactive electrophiles capable of being attacked by electron-rich nucleophiles and is widely used as the Vilsmeier formylation process. The Vilsmeier process has become more general, with the use of more varied amides, and has been particularly successful for the functionalization of pyrroles and indoles. Greater flexibility has been achieved with the replacement of phosphoryl chloride by trifluoromethanesulfonic anhydride. 

The Friedel-Crafts acetylation of 3-phenylsydnone was accomplished with boron trifluoride etherate as catalyst. Formylation at C-4 by the Vilsmeier procedure occurred with 3-phenylsydnone. Mercuration is easily afforded with mercury(II) acetate or mer-cury(13) chloride and thioethers can be made directly with DMSO in acetyl chloride (74T409). At least one fused ring as in compound (35) has been made by a coupling reaction on the sydnone (34) at C-4 (79JCS(P2)175l). 

The pyrilium salt 30a was obtained from benzo-9-crown-3 in 29% yield in two steps by formylation with hexamine in the presence of CF3CO2H, followed by reaction with 2 equiv of acetophenone in the presence of POCI3 <2002JOC2065>. In the same manner, the Vilsmeier formylation of the /V-phenyl dithiazonine and the subsequent condensation reaction with 2-aminobenzenethiol resulted in substituted benzothiazole 43 in 38% yield < 1999J(P2)1273>. Benzo-9-crown-3 ether trimerizes in the presence of fed and aqueous sulfuric acid to produce tris-(9-crown-3)-triphenylene 28 in 25% yield <2001CJC195>. 

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. 

While 5-formyluracils are easily accessible by a Vilsmeier formylation reaction, the first synthesis of 5-benzoyluracil could be achieved only by a multistep procedure involving lithiated pyrimidines (56JA2136 63JMC550). 

A new synthesis of olivacine 1138) (Scheme 24) and guatarabuine takes advantage of the stabilization of dihydropyridine derivatives by complexation with tricarbonylchromium(o). Thus, the readily prepared intermediate (139) gives a tricarfaonylchromiun complex (140), which can be formylated by the Vilsmeier procedure and dehydrogenated to demethylolivacine (141) this can be readily converted into olivacine and its N-methyl tetrahydro derivative, gua tambuine. ... 

Both substances yielded the 3-sulfonic acid (15% fuming sulfuric acid) and the 3-nitro compound (fuming nitric-sulfuric acid) neither 56 nor 57 could be formylated by the Vilsmeier procedure. 

Acylation can be conducted efficiently (a) with acid chlorides and SnCfi as catalyst to give 2-acylthiophenes and (b) by application of the Vilsmeier formylation to give thiophene-2-carbaldehydes ... 

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