Benzaldehyde, reaction + semicarbazide

Another interesting example is the aniline catalyzed formation of benzaldehyde semicarbazone [266]. Aniline and substituted anilines strongly accelerate the reaction of benzaldehyde with semicarbazide. The reaction rate and its pH dependence is equal to that of the formation of Schiff base from benzaldehyde and aniline (acid catalysis with changing rate-determining step) and does not depend on the concentration of semicarbazide. The final product is benzaldehyde semicarbazone, however. Obviously, benzaldehyde first reacts with aniline to form the Schiff base intermediate which then reacts rapidly with semicarbazide to form the semicarbazone. It has been established in separate experiments that the reaction of Schiff base with semicarbazide is fast. The detailed mechanism of the latter conversion is unknown. 

If we react equimolar amounts of acetaldehyde, benzaldehyde, and semicarbazide, the product initially formed will contain 99.5 % of acetaldehyde semicarbazone and only 0.5 % of benzaldehyde semicarbazone. Under these conditions, the reaction is subject to kinetic control, the products being determined by the rates at which they are formed since the backward reactions are much slower. If, however, the reaction mixture is allowed to stand, so that the backward reactions can take place and lead to equilibrium, the product now contains 90% of benzaldehyde semicarbazone and only 10% of acetaldehyde semicarbazone. The reaction is then said to be subject to thermodynamic control, the proportion of products being determined by their relative stabilities rather than their rates of formation. 

Further evidence in support of this proposed two-step mechanism was obtained by studying the reactions of a series of /lara-substituted benzaldehydes with semicarbazide to determine the electronic effects upon the individual steps of the reaction . The equilibrium con- stants for the formation of semicarbazide addition compounds show a Unear logarithmic correlation with Hammett s substituent constants, with a p value of +1-81. The aldehydes are therefore destabilized, relative to the addition intermediate, by electron-withdrawing substituents. The rates of acid-catalyzed dehydration show an almost equal and opposite p value of — 1-74, indicating that dehydration is euded by substituents capable of electron donation (Figure 3)... 

Consider the kinetic isotope effect that would be observed in the reaction of semicarbazide with benzaldehyde ... 

Problem 15.31 Reaction of 1 mole of semicarbazide with a mixture of 1 mol each of cyclohexanone and benzaldehyde precipitates cyclohexanone semicarbazone, but after a few hours the precipitate is benzaldehyde semicarbazone. Explain. ... 

The carbonyl group is a reactive function and, although aromatic aldehydes are somewhat less reactive than their aliphatic counterparts, benzaldehydes have an extensive chemistry. Many reactions replicate those of aliphatic aldehydes, but are mentioned here for completeness. Thus, oxidation of the carbonyl group leads to carboxylic acids and reduction gives alcohols. The aldehyde group reacts with a range of N-nucleophiles (Scheme 6.9). Imines (Schiff bases) are formed with amines and hydrazones with hydrazines. Semicarbazide gives semicarbazones and hydroxylamine forms oximes. 

As known from bioconjugate chemistry additional functional groups can be used for attachment of biomolecules. Thus, coupling via SH-groups [149,155,160], a benzaldehyde-semicarbazide-reaction [161] or the reaction between a streptavidin-coated surface and a biotinylated oligonucleotide [150,162,163] are only some examples. 

Most of these methods are applied to either PCR products or presynthesized oligonucleotides in combination with liquid-spotting systems. This allows control and optimization of the amount of the immobilized singlestrand [149]. SH-coupling or benzaldehyde-semicarbazide-coupling delivered maximal densities of approximately 10-100 pmol/cm [160,161], whereas binding of amino-functionalized PCR products to an aldehyde glass surface resulted in only 600 fmol/cm [154], However, only 10-30% of the immobilized probes took part in the hybridization reaction so that the optimal probe density was even further reduced [149]. The density of spots in these arrays is limited by mechanical constraints of liquid delivery or surface manipulation. 

In addition, this synthetic scheme offers a mild reaction route for the degradation of a-hydroxy acids to the corresponding aldehydes containing one less carbon atom or for their conversion to aldehydes with the same number of carbon atoms. For example, reaction of 1,4-diphenylthio-semicarbazide with a-acetoxyacyl chlorides yields 5-(a-hydroxyalkyl)-1,2,4-triazolium salts, which, upon sodium hydride reduction and acid treatment, give benzaldehyde along with 138 (R = H) (Scheme 58) (75TL1889). Moreover, the 5-(a-hydroxyalkyl)-l,2,4-triazolium salts can be easily converted to the 5-alkyl compounds (Scheme 58) and borohydride reduction of the latter followed by acid hydrolysis provides a method for the transformation of a-hydroxy acids to aldehydes with the... 

If the overall reaction followed the BEP principle, the rate of formation of a given semicarbazone should be greater, the more stable it is. In other words, the rate constants for the forward reaction should run parallel to the corresponding equilibrium constants K. This is not the case, as the results in Table 5.1 show. Thus acetaldehyde reacts nearly 200 times faster with semicarbazide than does benzaldehyde, but the equilibrium constant favors benzaldehyde semicarbazone by a factor of ten. 

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