Thermal-catalyzed condensation

Thermal or acid-catalyzed condensation of anilines with P-ketoesters leads to qui-... 

Isodehydroacetic acid has been prepared by the action of sulfuric acid on acetoacetic ester 3 4 The ethyl ester has been prepared by the action of dry hydrogen chloride on acetoacetic ester 6 6 and by the sodium-catalyzed condensation of ethyl /3-chloroisocrotonate with ethyl acetoacetate3 The methyl ester of isodehydroacetic acid has been prepared by the thermal rearrangement of pyrazolines 7... 

The base-catalyzed condensation of a-azido esters and ketones with aromatic aldehydes has recently been developed as a new vinyl azide synthesis.42,43 The yields range from moderate to excellent in some cases. The thermal decomposition of ethyl a-azidocinnamate (87) in xylene gives only 2-ethoxycarbonylindole (88).44 The unstable 2-ethoxycarbonyl-3-phenyl-l-azirine could be detected if the thermolysis was carried out at a lower temperature. This fact indicates that the 1-azirine is probably an intermediate leading to the indole, although the intermediacy of the vinyl nitrene could not be established. This result is similar to that observed by Isomura et al. on the pyrolysis of terminal vinyl azides.27,28... 

Compound 50c was obtained in ca. 25% yield as a precipitate from the acid-catalyzed condensation of pyrogallol and isovaleraldehyde. No evidence of any hexamer was found in the solid material. To convert this material into the hexamer (50c)6, the original precipitate can be dissolved in Et20, acetone, or methanol, with a few drops of nitrobenzene or o-dinitrobenzene, followed by crystallization upon slow evaporation. The hexamer may also be obtained by thermal treatment of the initial precipitate or the initial filtrate. The product in the initial filtrate may be converted into hexamer by extraction in Et20, followed by evaporation to dryness with subsequent dissolution in methanol. The methanol solution is then heated to 120-150 °C for at least 12 h. Methanol may be removed under vacuum to yield a red-brown solid. Colorless hexameric spherical capsules are obtained from this solid utilizing the crystallization procedure described for the initial precipitate. 

Two key intermediates in the production of vitamin A are citral and the so-called C5 aldehyde. In the modem routes to these intermediates, developed by BASF and Hoffmann-La Roche, catalytic technologies are used (see Fig. 2.29 and 2.30). Thus, in the synthesis of citral, the key intermediate is 2-methyl-l-butene-4-ol, formed by acid-catalyzed condensation of isobutene with formaldehyde. Air oxidation of this alcohol over a silver catalyst at 500°C (the same catalyst as is used for the oxidation of methanol to formaldehyde) affords the corresponding aldehyde. Isomerization of 2-methyl-l-butene-4-ol over a palladium-on-charcoal catalyst affords 2-methyl-2-butene-4-ol. The latter is then reacted with the aldehyde from the oxidation step to form an enol ether. Thermal Claisen rearrangement of the enol ether gives citral (see Fig. 2.29). 

Alkyl vinyl ketones were synthesized in 1906 by heating (3-chloroethyl ketones with diethylaniline [327]. A large number of syntheses have been developed since that time, but only three or four have general applicability. Most syntheses are carried out at a low pH value to minimize the base-catalyzed condensation of the vinyl ketones. However, a rather elegant synthetic route for alkyl vinyl ketones involves a base catalyzed condensation of formaldehyde with methyl or ethyl ketones, respectively. Thermal dehydration of the p-ketoalcohol intermediates in the presence of weak acid catalysts produced a,p-unsaturated ketones in 50 to 60% yields. Several variations of this procedure have been reported [328]. 

Azido esters such as 10 are readily prepared from the corresponding aldehyde by phos-phonate condensation. Shunsuke Chiba and Koichi Narasaka of Nanyang Technology University demonstrated (Organic Lett. 2008, 10, 313) that thermal condensation of 10 with acetyl acetone 11 gave the pyrrole 12, while Cu catalyzed condensation with acetoac-etate 13 gave the complementary pyrrole 14. 

Recently, two important variations of the condensation polymerization approach to poly(phosphazenes) have been reported. The first involves an alternate synthetic route to poly(dichlorophosph ene) via the thermal elimination of phosphoryl chloride firom a P-N=P precursor (equation 1). The second (8) involves the catalyzed condensation polymerization of certain N-silylphosphoranimines (equation 2) to afford various aUcoxy- and/or aiyloxy-substituted poly(phosphazenes). 

There also exists an acidregioselective condensation of the aldol type, namely the Mannich reaction (B. Reichert, 1959 H. Hellmann, 1960 see also p. 291f.). The condensation of secondary amines with aldehydes yields Immonium salts, which react with ketones to give 3-amino ketones (=Mannich bases). Ketones with two enolizable CHj-groupings may form 1,5-diamino-3-pentanones, but monosubstitution products can always be obtained in high yield. Unsymmetrical ketones react preferentially at the most highly substituted carbon atom. Sterical hindrance can reverse this regioselectivity. Thermal elimination of amines leads to the a,)3-unsaturated ketone. Another efficient pathway to vinyl ketones starts with the addition of terminal alkynes to immonium salts. On mercury(ll) catalyzed hydration the product is converted to the Mannich base (H. Smith, 1964). 

Phosphoms-containing additives can act in some cases by catalyzing thermal breakdown of the polymer melt, reducing viscosity and favoring the flow or drip of molten polymer from the combustion zone (25). On the other hand, red phosphoms [7723-14-0] has been shown to retard the nonoxidative pyrolysis of polyethylene (a radical scission). For that reason, the scavenging of radicals in the condensed phase has been proposed as one of several modes of action of red phosphoms (26). 

Alternatively, thermal cracking of acetals or metal-catalyzed transvinylation can be employed. Vinyl acetate or MVE can be employed for transvinylation and several references illustrate the preparation especially of higher vinyl ethers by such laboratory techniques. Special catalysts and conditions are required for the synthesis of the phenol vinyl ethers to avoid resinous condensation products (6,7). Direct reaction of ethylene with alcohols has also been investigated (8). 

The Pictet-Spengler reaction is one of the key methods for construction of the isoquinoline skeleton, an important heterocyclic motif found in numerous bioactive natural products. This reaction involves the condensation of a P-arylethyl amine 1 with an aldehyde, ketone, or 1,2-dicarbonyl compound 2 to give the corresponding tetrahydroisoquinoline 3. These reactions are generally catalyzed by protic or Lewis acids, although numerous thermally-mediated examples are found in the literature. Aromatic compounds containing electron-donating substituents are the most reactive substrates for this reaction. 

The approach was carried out on a ketohexo backbone bearing acid-sensitive ketal groups (Scheme 29). l,2 4,5-Di-0-isopropylidene-/ -D-fructo-pyranose readily underwent PDC oxidation of the 3-OH, followed by selective acid-catalyzed hydrolysis of the 4,5-ketal to afford a partially protected ketone in 94% overall yield. For the subsequent HSCN condensation, adapted acidic conditions had to be established to avoid 1,2-isopropylidene cleavage under thermal conditions and the target OZT (R = H) could be isolated in 60% yield. When performed in ethanol, the condensation afforded the acetalic counterpart (R = Et) albeit in lower yield. 

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