Aldol condensation catalytic

DIBK can be produced by the hydrogenation of phorone which, in turn, is produced by the acid-catalyzed aldol condensation of acetone. It is also a by-product in the manufacture of methyl isobutyl ketone. Diisobutyl ketone ( 1.37/kg, October 1994) is produced in the United States by Union Carbide (Institute, West Virginia) and Eastman (Kingsport, Teimessee) (47), and is mainly used as a coating solvent. Catalytic hydrogenation of diisobutyl ketone produces the alcohol 2,6-dimethyl-4-heptanol [108-82-7]. 

Oxadiazoles, 6, 365-391 aldol condensation, 6, 383 bond lengths, 6, 378 catalytic hydrogenation, 5, 75 chemotherapy, 6, 391 dipole moments, 6, 378 electron densities, 6, 378 electrophilic substitution, 6, 382 ethers... 

An alternate scheme for preparing these compounds starts with a prefabricated pyrimidone ring. Aldol condensation of that compound (95), which contains an eneamide function, with pyridine-3-aldehyde (80), gives the product 96. Catalytic hydrogenation gives the product of 1,4 reduction. The resulting pyrimidinedione, of course exists in the usual tautomeric keto (97a) and enol (97b) forms. Reaction with phosphorus oxyxchloride leads to the chloro derivative 98. Displacement with methoxide gives 99. Reaction of this last intermediate with the furylalkylamine derivative 92 leads to the H-2 blocker lupitidine (100) [22]. 

Pyrimidinopyrazines related to folic acid have been investigated in some detail for their antimeta-bolic and antineoplastic activities. A related compound, which lacks one nitrogen atom, has been described as an antiproliferative agent, indicating it too has an effect on cell replication. Aldol condensation of the benzaldehyde 99 with ethyl acetoacetate gives the cinnamate 100. This is then reduced catalytically to the acetoacetate 101. Reaction of that keto ester with 2,4,6- triami-nopyrimidine gives the product 102 which is subsequently chlorinated (103) and subjected to hydrogenolysls. There is thus formed piritrexim (104) [17]. 

The aldol reaction can be applied to dicarbonyl compounds in which the two groups are favorably disposed for intramolecular reaction. Kinetic studies on cyclization of 5-oxohexanal, 2,5-hexanedione, and 2,6-heptanedione indicate that formation of five-membered rings is thermodynamically somewhat more favorable than formation of six-membered rings, but that the latter is several thousand times faster.170 A catalytic amount of acid or base is frequently satisfactory for formation of five- and six-membered rings, but with more complex structures, the techniques required for directed aldol condensations are used. 

For example, large rate enhancements have been reported in the synthesis of chal-cones by crossed-aldol condensations in open vessels, suggesting the participation of specific MW effects [41]. The chalcone 24 was synthesized from cyclohexanone and benzaldehyde in ethanol, in the presence of a catalytic amount of sodium hydroxide (Scheme 4.13), in a MW oven in 90% yield in only 1 min. 

This possible mechanism should be evaluated in relation to the catalysts. If the catalytic action is to be ascribed to the acid character of the catalysts, the condensation under consideration may differ from the ordinary aldol condensation, which is catalyzed preferentially by basic agents. Nevertheless, many condensations of the aldol type are effected with the aid of acidic reagents. Moreover, the condensation of sugars with dicarbonyl compounds has been carried out in aqueous alcoholic media which are non-acidic hence, there also exists the possibility of a mechanism catalyzed simultaneously by acid and by base, somewhat like that suggested by Lowry46 in another connection. A transition state with an amphiprotic structure has been postulated. Its formation can be catalyzed by either acids or bases. 

Van Koten and Frey used a hyperbranched poly(triallylsilane) as the support for palladium- pincer complexes.[63] The supported palladium-pincer complexes were applied in the catalytic aldol condensation of benzaldehyde and methyl isocyanate. Their activity was similar to that of single site Pd catalysts. According to the authors, the complex is suitable for continuous membrane applications, as demonstrated by their purification by means of dialysis. 

The condensation of aldehydes and ketones with aminoacetonitriles, although it requires more vigorous soliddiquid catalytic conditions to produce the cyano-enamines, is preferable in many respects to the traditional Wittig-Horner or Peterson procedures [45]. Hydroxyalkylphosphonates are obtained from the catalysed aldol condensation of nitromethane with acylphosphonates [46]. 

Finally, another possibility is to design enantioselective syntheses by using external chiral auxiliaries either in catalytic or in stoichiometric quantities [21], Since these strategies are nowadays of great interest in organic synthesis, we will consider here some of the most recent results achieved in enantioselective aldol condensations, as well as in the asymmetric epoxidation and hydroxylation of olefmic double bonds. 

Table 9.6 shows the effect of both the addition time and the polarity of the solvent, as well as the nature of the aldehyde, in the catalytic asymmetric aldol condensation promoted by tributyltin fluoride and a chiral diamine coordinated to tin(n) triflate. 

Tandem 1,4-addition to cycloalkenones constitutes an extremely versatile and elegant methodology for the synthesis of 2,3-disubstituted cycloalkanones, as is evident from its application in areas such as prostaglandin synthesis. Noyori et al. have reported the use of organozinc reagents in copper-catalyzed tandem additions [64]. The zinc enolate resulting from the catalytic enantioselective 1,4-addition of Et2Zn to cyclohexenone reacts readily with an aldehyde in a subsequent aldol condensation. 

Trost s group reported direct catalytic enantioselective aldol reaction of unmodified ketones using dinuclear Zn complex 21 [Eq. (13.10)]. This reaction is noteworthy because products from linear aliphatic aldehydes were also obtained in reasonable chemical yields and enantioselectivity, in addition to secondary and tertiary alkyl-substituted aldehydes. Primary alkyl-substituted aldehydes are normally problematic substrates for direct aldol reaction because self-aldol condensation of the aldehydes complicates the reaction. Bifunctional Zn catalysis 22 was proposed, in which one Zn atom acts as a Lewis acid to activate an aldehyde and the other Zn-alkoxide acts as a Bronsted base to generate a Zn-enolate. The... 

Application of an organocatalytic domino Michael addition/intramolecular aldol condensation to the preparation of a series of important heterocycles has recently received much attention [158] with methods being disclosed for the preparation of benzopyrans [159-161], thiochromenes [162-164] and dihydroquinolidines [165, 166]. The reports all use similar conditions and the independent discovery of each of these reactions shows the robust nature of the central concept. A generalised catalytic cycle which defines the principles of these reports is outlined in Fig. 10. Formation of iminium ion 102 is followed by an intermolecular Michael addition of an oxygen, sulfur or nitrogen based nucleophile (103) to give an intermediate... 

Fig. 10 Catalytic cycle for the organocatalytic domino Michael/intramolecular aldol condensation...

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