Cross-condensation

CH2 CH CH0. a colourless, volatile liquid, with characteristic odour. The vapour is poisonous, and intensely irritating to eyes and nose b.p. 53"C. It is prepared by the distillation of a mixture of glycerin, potassium sulphate and potassium hydrogen sulphate. It is manufactured by direct oxidation of propene or cross-condensation of ethanal with meth-anal. 

The alkylphenylacetyi chloride 843 and benzoyl chloride undergo decarbo-nylative cross-condensation to give the enone 845 in the presence of EtiNf723]. The reaction is e.xplained by the insertion of the ketene 844 into the Pd-aryl bond and, 3-elimination. To support this mechanism, o, d-unsaturuted ketones are obtained by the reaction of ketenes with aroyl chlorides[724]. 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

A two-step sequence of nitrile oxide-olehn cycloaddition and reduction of the resulting A -isoxazolines offers a unique and attractive alternative to the classical aldol reaction and its many variants (2J). The procedure bypasses traditional problems, including enolate equilibrium and cross condensation (20). 

The second route gave 84% of TM(35). There is no problem with the cross condensation as only acetone can enolise and (36) has the more reactive carbonyl group. Synthe s-is ... 

There are many possibilities and I shall simply analyse the published synthesis. Removal of the methyl group from (50) gives ketone (51) which can be made from enone (52) by Michael addition of an ethyl group. Unambiguous cross-condensation between enolisable (54) and reactive (53) gives (52). 

The cross-condensation reaction of benzyl benzoate (46) and 44 was carried out under solvent-free conditions. Treatment of a 1 1 mixture of 46 and 44a with Bu OK at 120 °C for 1 h gave the cross-condensed product 47a in 42% yield (Scheme 7). Similar reaction of 46 with 44b gave 47b in 45% yield. Because heating of46,44, and Bu OK in toluene under reflux for 16 h did not give any product, it is clear that the solvent-free reaction is again effective for the cross-condensation. In these cases, self-condensation of 44 itself did not occur probably because of the high reactivity of 46 [9]. 

The selective dimerization of aldehydes to esters [236] as well as the cross-condensation of cycloalkanones with aldehydes and primary alcohols [237] were found to proceed very efficiently under mild conditions with 1 as catalyst (Scheme 8-33). 

Scheme 8-33 [Cp2Zr(H)CI] 1-catalyzed cross-condensation reactions...

The synthetic methods of symmetrically substituted Pcs are similar to those of the parent unsubstituted Pcs. However, unsymmetrically substituted Pcs are usually prepared by statistical condensation methods, subphthalocyanine expulsion methods or cross-condensation methods. 

The unsymmetrical thiacrown porphyrazines Mg[pz(A3B)], where A = Bn, B = S3 (92a) and Mg[pz(A3B)], where A = Bn, B = S4 crown (93a) were formed by a cross-condensation of excess 3,6-dibutyl-1,2-dicyanobenzene and the corresponding thiaether crown dithiomaleonitrile derivative (91). The porphyrazines were demetalated with TFA and remetalated with either copper or nickel acetate to form Compounds 92c, 93c and 93d (16-18%). 

Other unsymmetrical aminoporphyrazines have been prepared accordingly. The base-catalyzed cross-condensation of bis(dimethylamino)maleonitrile (99) with 1,2-dicyanobenzene (132) produced a statistical mixture of six possible products that represent hybrids between a heterosubstituted aminoporphyrazine and pc (9). The individual yields of all six products depend on the molar ratio of both starting dinitriles. For instance, a 25 1 ratio of dinitriles 99 and 132 produced mainly pz 133 (35%) along with 100 (Scheme 23). 

An exceptionally mild procedure for the cross-condensation of aldimines and enolsilanes has been described (eq. [67]) (80). This titanium tetrachloride-mediated reaction is predicated on the previous analogies provided by Mukaiyama for related aldol condensations (73a). Depending on aldimine structure and reaction time, either -lactams or their penultimate amino esters may be isolated from the reaction. The authors postulate that these reactions are proceeding via titanium enolates derived from ligand exchange by... 

A related report has demonstrated that aldehydes can be converted into esters in the presence of allylic alcohols [83]. Dihydrocinnamaldehyde 91 and aUyl alcohol 95 undergo a cross-condensation reaction to give ester 96. The allyl alcohol 95 also serves as a hydrogen acceptor, perhaps via an isomerization/reduction sequence (Scheme 23). 

Several cross-aldol condensations have been performed with alkaline earth metal oxides, including MgO, as a base catalyst. A general limitation of the cross-aldol condensation reactions is the formation of byproducts via the self-condensation of the carbonyl compounds, resulting in low selectivities for the cross-aldol condensation product. For example, the cross-condensation of heptanal with benzalde-hyde, which leads to jasminaldehyde (a-K-amylcinnamaldehyde), with a violet scent... 

Another important example is the cross-aldol condensation of citral and acetone, which yields pseudoionone (Scheme 14), an intermediate in the commercial production of vitamin A. Numerous commercial routes to the preparation of pseu-doionones are based on the aldol condensation using conventional homogeneous catalysts, such as aqueous alkali metal hydroxide solutions, alcoholates in alcohol or benzene solvents (126-129). The yields of the cross-condensation product vary between 50% and 80%, depending on the type of catalyst and conditions such as catalyst concentration, ratio of reagents, and temperature. 

Cross condensations with molecules which cannot enolise. 

Use of compounds with no enolisable protons. Methods of avoiding ambiguity in cross condensations. ... 

In this procedure acyclic methyl ketones condense almost exclusively at the methyl group. Rnoli/ablc a,/ -enals also undergo efficient cross condensation with methyl kcloncs.1... 

Bisdehydrothia-annulene (94) and the annulated bisdehydrooxa- and thia-annulenes (99 and 100) were synthesized73 in two steps as shown in Scheme 4, the key initial step entailing cross-condensation of 45 with properly designed dialdehydes. Acyclic models (93, 97, and 98) were reported to be quite unstable, and this appears to have prevented their... 

If, however, it is necessary to generate a crossed product by the reaction of an enolate derived from one carbonyl compound with a second carbonyl compound as the electrophile, tilings can go bad rapidly. Because both carbonyl groups must be present in solution at the same time and each can form etiolates to some extent, there can be four possible products from the various combinations of etiolates and carbonyl compounds. This problem was illustrated for the crossed-Claisen condensation above. The number of products can be minimized if one carbonyl component lacks a protons and cannot form an enolate and is also a more reactive electrophile than the second carbonyl component. If these conditions are met, then crossed condensations can be carried out successfully using alkoxide bases. Many of the named reactions were developed so that product mixtures could be avoided. 

Cross-Condensation III Removal of a Product from Equilibrium... 

The resulting furfurals then can undergo a series of complicated polymerization reactions. Hodge (8) reported that these reactions include hydrolytic fission, fission of 2-ketoses, dehydration of triose, dismutation of biose, trioses, and tetroses, self- and cross-condensations of aldehydes and ketones, reversion of aldoses and ketoses to various oligosaccharides, dimerization of monosaccharides, cyclodehydration of aldoses followed by polymerization, and finally, the enolization and dehydration of formed oligosaccharides. 

It has been found that low-valent iridium hydride complexes are effective catalysts for activation of both the a-C-H bond and the CN triple bond of nitrile. Actually, the catalytic cross condensation of nitrile 27 and nitrile 28 in the presence of IrH(CO)(PPh3)3 catalyst (29) was performed under neutral conditions to give the... 

When acetone is treated with excess benzaldehyde in the presence of base, the crossed condensation adds two equivalents of benzaldehyde and expels two equivalents of water. Propose a structure for the condensation product of acetone with two molecules of benzaldehyde. 

Crossed Clsisen only one of the esters has the a hydrogens needed to form an enolate. In a crossed Condensations Claisen condensation, an ester without a hydrogens serves as the electrophilic component. Some useful esters without a hydrogens are benzoate, formate, carbonate, and oxalate esters. 

So far we have considered only self-condensations1—dimerization reactions of a single carbonyl compound. These form only a tiny fraction of known aldol reactions. Those that occur between two different carbonyl compounds, one acting as a nucleophile in its enol or enolate form, and the other as an electrophile, are called cross-condensations. They are more interesting than self-condensations, but working out what happens needs more thought. 

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