Aldehydes with active hydrogen

The imide nitrogen atom was also most reactive to a variety of electrophilic species (hydrogen halides, pseudohalogens, and alkyl halides) in the parent Rimidophosphazenes, R(C—NH)-N=PPh3. With t-butyl hypochlorite the /V-chloro-derivatives, R(C=NCl)-N=PPh3, were obtained. R/ -Vinyl-phenylphosphazenes have been prepared by condensation of aldehydes with active methylene compounds ... 

The condensation of aldehydes and ketones with active hydrogen atoms is called Knoevenagel condensation. It is related to an aldol condensation and commonly is used to produce enones (a compound with a carbon-carbon double bond adjacent to a carbonyl). The process requires a weak base (an amine). A typical excimple and mechanism eire presented in Figure 15-22. 

In 1952, it was discovered by Schiller that rhodium salts generated highly active hydroformylation catalysts. It was from these early studies that rhodium was estimated to be 1000 to 10 000 times more active than cobalt. Rhodium was also found to be very selective to aldehydes, with httle hydrogenation to alcohols observed under normal catalysis conditions. It was suggested early on that HRh(CO)4 was the active catalyst species, analogous to HCo(CO)4, and the same monometallic mechanism was proposed (Scheme 6). 

Reaction of butadiene with aldehydes in the presence of palladium(o)-triphenylphosphine species leads to two products (80) and (81), whose formation can be explained by the mechanism outlined in Scheme 4. Whereas butadiene reacts with active-hydrogen-containing compounds such as a-cyano-esters or jS-diketones in the presence of palladium complexes of unidentate phosphines, in the presence of palladium complexes of bidentate phosphines addition of the butadiene to the active-hydrogen compound takes place. ... 

The yield of the more active RRR-a-tocopherol can be improved by selective methylation of the other tocopherol isomers or by hydrogenation of a-tocotrienol (25,26). Methylation can be accompHshed by several processes, such as simultaneous halo alkylation and reduction with an aldehyde and a hydrogen haUde in the presence of staimous chloride (27), amino alkylation with ammonia or amines and an aldehyde such as paraformaldehyde followed by catalytic reduction (28), or via formylation with formaldehyde followed by catalytic reduction (29). 

The procedure is modified for the reaction of preformed cyanohydrins with chiral amines39. I11 a further variation, Schiff bases of aliphatic aldehydes with optically active 1-arylalkyl-amines are transformed with liquid hydrogen cyanide to the corresponding a-aminonitrilcs, which, after acid hydrolysis, give the /V-aryUilkylamino acids. Hydrogenation then yields the a-amino acids40 41. 

If the active hydrogen compound has two or three active hydrogens, the Mannich base may condense with one or two additional molecules of aldehyde and ammonia or amine, for example. 

Organic compounds containing active hydrogen atoms adjacent to a carbonyl group (aldehydes, ketones, carboxylic acids) may react violently in unmoderated contact with bromine. 

Aldehydes may participate in a condensation reaction with an amine compound and a substance containing a sufficiently-active hydrogen, yielding an alkylated derivative that effectively... 

In its simplest form, the Mannich reaction consists of the condensation of formaldehyde (or sometimes another aldehyde) with ammonia, in the form of its salt, and another compound containing an active hydrogen. Instead of using ammonia, however, this reaction can be done with primary or secondary amines, or even with amides. An example is illustrated in the condensation of acetophenone, formaldehyde, and a secondary amine salt (the active hydrogens are shown underlined) ... 

Gordon used a household microwave oven for the transfer hydrogenation of benz-aldehyde with (carbonyl)-chlorohydridotris-(triphenylphosphine)ruthenium(II) as catalyst and formic acid as hydrogen donor (Eq. 11.43) [61]. An improvement in the average catalytic activity from 280 to 6700 turnovers h-1 was achieved when the traditional reflux conditions were replaced by microwave heating. 

Attempted reaction of 1,3-pentadiene with the optically active diboron derived from dialkyl tartrate in the presence of a phosphine-free platinum catalyst gave poor diastereoselectivity (20% de).63 Better selectivity has been attained with a modified platinum catalyst bearing a PCy3 ligand (Scheme 6).64 The reaction of allylborane thus obtained with an aldehyde followed by oxidation with basic hydrogen peroxide affords the corresponding diol derivative with moderate ee. 

Bianchini and coworkers [126] found a difference in the chemoselectivity between the metals Fe, Ru, and Os in the complexes [M(H2)H(P(CH2CH2PPh2)3)]-BPh4 in the hydrogenation of benzylideneacetone by transfer from iso-propanol. The Fe and Ru catalysts reduced the 0=0 bond to give the allyl alcohol, with Ru more active than iron (TOF 79 IT1 at 60°C for Ru versus 13 IT1 at 80°C for Fe), while the Os catalyst first reduced the 0=0 bond but then catalyzed isomerization of the allyl alcohol to give the saturated ketone (TOF 55 IT1 at 80°C). The difference in reactivity was attributed to the weak binding of the alkene of the allyl alcohol to Fe and Ru relative to Os in these complexes. A variety of selec-tivities was noted for other unsaturated ketones, whereas unsaturated aldehydes were not hydrogenated. 

Multicomponent reaction systems are highly valued in solid-phase organic synthesis because several elements of diversity can be introduced in a single transformation.1 The Mannich reaction is a classic example of a three-component system in which an active hydrogen component, such as a terminal alkyne, undergoes condensation with the putative imine species formed from the condensation of an amine with an aldehyde.2 The resultant Mannich adducts contain at least three potential sites for diversification specifically, each individual component—the amine, aldehyde, and alkyne—can be varied in structure and thus provide an element of diversity. 

Since then, optically active a-aminophosphonates have been obtained by a variety of methods including resolution, asymmetric phosphite additions to imine double bonds and sugar-based nitrones, condensation of optically active ureas with phosphites and aldehydes, catalytic asymmetric hydrogenation, and 1,3-dipolar cycloadditions. These approaches have been discussed in a comprehensive review by Dhawan and Redmore.9 More recent protocols involve electrophilic amination of homochiral dioxane acetals,10 alkylation of homochiral imines derived from pinanone11 and ketopinic acid,12 and alkylation of homochiral, bicyclic phosphonamides.13... 

The hydrogenation activity is an added advantage of this route, since most of the hydroformylation-products are converted to the alcohols anyway. Concurrent with the hydrogenation of aldehyde to alcohol, however, hydrogenation of alkene feedstock to alkane occurs, which may be as high as 15% under certain conditions (versus 2-3% for the non-ligand-modified... 

It is to be mentioned that water-soluble phosphine complexes of rhodium(I), such as [RhCl(TPPMS)3], [RhCl(TPPTS)3], [RhCl(PTA)3], either preformed, or prepared in situ, catalyze the hydrogenation of unsaturated aldehydes at the C=C bond [187, 204, 205]. As an example, at 80 °C and 20 bar H2, in 0.3-3 h cinnamaldehyde and crotonaldehyde were hydrogenated to the corresponding saturated aldehydes with 93 % and 90 % conversion, accompanied with 95.7 % and 95 % selectivity, respectively. Using a water/toluene mixture as reaction medium allowed recycling of the catalyst in the aqueous phase with no loss of activity. 

Copper-containing amine oxidases (non-blue copper proteins) catalyze the oxidative deamination of primary amines to the corresponding aldehydes with the release of ammonia and concomitant reduction of oxygen to hydrogen peroxide. They typically use a quinone redox cofactor [topaquinone (TPQ)], which is bound covalently in the active site, and are thought to form a Cu(I)-TPQ semi-quinone radical intermediate during the redox reaction [13]. 

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