3-Acetyl-2, 4-dimethylpyrrole

Azaferrocene (206) has been prepared by the reaction of sodium pyrrole, cyclopentadienylsodium, and ferrous chloride,157 or better by the reaction of potassium pyrrole with cyclopentadienyliron dicarbonyl iodide.158 It has been found159 that dioxane is a better solvent than benzene for this latter reaction. This reaction has also been applied to 2,4- and 2,5-dimethylpyrrole,158 3-acetyl-2-methyl-and 3-acetyl-2,4-dimethylpyrrole,160 and 2-methylpyrrole.159 The 2-methylazaferrocene from this latter pyrrole has been resolved with (—)6,6 -dinitrodiphenic acid.159 A compound (207) believed to be an intermediate in the formation of azaferrocenes has been isolated.161... 

A suspension of benzyl 2-acetoxymethyl-3-(2-methoxycarbonylethyl)-4-methyl-pyrrole-5-carboxylate and 3-acetyl-2,4-dimethylpyrrole in methanol treated with p-toluenesulfonic acid hydrate, and warmed 4 hrs. at 35 under Ng -> product. Y 91%. F. e., also tripyrranes, s. A. M. d A. Rodia Gonsalves, G. W. Kenner, and K. M. Smith, Tetrah. Let. 1972, 2203. 

Of many substituted pyrroles showing CNS depressant effects in rodents, 3-acetyl-2,4-dimethylpyrrole (11) was selected for study as a tranquilizer and muscle relaxant in man. Side effects precluded going to doses large enough to observe desired effects ... 

Discrepancies have also been reported165 for 2-acetyl-5-ethoxy-carbonyl-3,4-dimethylpyrrole, which shows two vNH absorption bands, and for 2,5-diacetylpyrrole, which exists predominantly as 6947 and shows only one band in the 3500-3400 cm-1 region.166... 

The 1-methylpyrrole complex 21 undergoes clean acylation at the P-position in the presence of Ac20/DMAP to give the 3-acetyl-1-methylpyrrole complex, 38 (Figure 10).12b Propionic anhydride reacts with 21 in a similar manner to form 39. Under these reaction conditions, the parent pyrrole complex (20) undergoes exclusive A-acylation to give 40, and the 2,5-dimethylpyrrole complex (22) gives a 7 3 ratio of N- to P-acylation. 

Pyrroles and furans also undergo the Gattermann aldehyde synthesis with HC1 and HGN, furan gives furfuralde-hyde. The HoubenHoesch ketone synthesis is also applicable to the preparation of acyl derivatives of furans and pyrroles, e.g., ethyl 2,4-dimethylpyrrole-3-carboxylate with MeCN and HC1 yields ethyl 5-acetyl-2,4-dimethyl-3-carboxylate. 

RCOCHjR — RCOC( = NOH)R RCOCH(NHj)R. An example is the condensation of ethyl a-aminoacetoacetate (Ri = COjC2Hs, R2 = CHj) with acetoacetic ester (Rj = C02C2Hs, R4 = CHj) to give 2,4-dimethyl-3,5-dicarbethoxypyrrole (64%). The synthesis of 3-acetyl 5-carbethoxy-2,4-dimethylpyrrole from ethyl acetoacetate and acetylacetone also illustrates the procedure. ... 

Pyrrole itself undergoes a,a -disubstitution. Diazo-acetoacetic ester can be used in this reaction. The mechanism of this reaction, which may be a radical substitution or involve the intermediate formation of a ketene, is uncertain, but it is interesting to note that a number of pyrroles react readily with diketene, giving G-acetoacetyl derivatives, and that ketene converts 2,4-dimethylpyrrole into 2-acetyl-3,5-dimethylpyrrole . In view of these results, the earlier report that diphenylketene converted pyrrole into 1-diphenylacetylpyrrole must be questioned. 

Chemical evidence is never unequivocal in indicating the position of a tautomeric equilibrium. For a number of both a- and jS-hydroxypyrroles, physical data are available. Thus, comparison of the ultra-violet spectra of the compounds (96) with those of their necessarily pyrrolic O-acetyl esters (97) proves clearly the predominance of the oxopyrroline forms in ethanol H. In contrast, the chemical evidence is confused the compounds are soluble in alkali, give no ferric reaction, give benzylidene derivatives, do not react with diazomethane and undergo both O- and C-acetylation. The formulation of 2-hydroxy-3,4-dimethylpyrrole as 3,4-dimethyl-2-oxo-J -pyn-oline (98) is supported by proton resonance data ss. In contrast, the formyl group appears to stabilize the hydroxy form (99) 55. O-Ethylation of (98) is conveniently effected by triethyloxonium borofluoride se. 

Some studies have been carried out on the specificity of the condensation reaction using synthetic monopyrroles. In addition to 2,4-dimethylpyrrole, other pyrroles, such as 2,4-dimethyl-3-ethylpyrrole (kryptopyrrole) and 2-methyl-pyrrole, condensed with MBC in growing cultures or in resting cell suspensions of 9-3-3 (Williams, 1965 Williams and Goldschmidt, unpublished). No pigment was formed if the monopyrrole was 2,5-dimethylpyrrole, 2,4-dimethyl-3-acetyl-pyrrole or unsubstituted pyrrole. 

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