Propionaldehyde, protonated

The acidic and adsorptive properties of the samples in gas phase were evaluated in a microcalorimeter of Tian-Calvet type (C80, Setaram) linked to a volumetric line. For the estimation of the acidic properties, NH3 (pKa = 9.24, proton affinity in gas phase = 857.7 kJ.mol-1, kinetic diameter = 0.375 nm) and pyridine (pKa = 5.19, proton affinity in gas phase = 922.2 kJ.mol-1, kinetic diameter = 0.533 nm) were chosen as basic probe molecules. Different VOC s such as propionaldehyde, 2-butanone and acetonitrile were used in gas phase in order to check the adsorption capacities of the samples. 

In the examples of reductions of XCH2CHO mentioned above, hydration occurs both as antecedent and interposed reactions. The change of the second reduction step with pH is similar to that observed for acetaldehyde, but not quantitatively identical. This indicates that the second dehydration step is preceded here by a proton transfer. The rate of the proton transfer involving the carbanion formed as a primary electrolysis product governs the height of the acetaldehyde wave 84, 85). In the reduction of cinnamaldehyde, where only the hydration is interposed between the reductions of cinnamaldehyde and of 3-phenyl-propionaldehyde 87), the pH-dependence of the more negative wave of cinnamaldehyde is quantitatively identical with the pH-dependence of... 

S)-proline-catalyzed reaction using propionaldehyde as donor and the results showed that the imine reactivity was approximately sevenfold higher than that of the aldehyde [83]. Under basic conditions, it is generally accepted that nucleophilic addition to an aldehyde is typically faster than addition to an aldimine, but nucleophilic addition to an aldimine is faster than addition to an aldehyde when protonation of the imine nitrogen occurs [83]. In the (S)-proline-catalyzed three-component Mannich reactions in the absence of arylaldehyde, self-Mannich products were obtained with moderate to high diastereo- and enantioselectivities (Scheme 2.19) [71b, 82]. 

Reaction of ethyl 2,5-butadienoate with aldehydes.1 This ester (1) reacts with propionaldehyde in ether at 23° in the presence of DABCO to provide 2 in 42% yield, formed by replacement of the a-proton of 1. This condensation can also be effected with butyllithium, but then 2 is accompanied by 3, formed via a dianion of 1. 

By contrast, substitution in position 7 is much easier thanks to the well-known Minisci reaction, which involves a nucleophilic radical attack on a protonated quinoline [31]. Moreover, due to the unavailability of position 2 of the quinoline nucleus, the reaction shows complete regioselectivity. Minisci alkylation with an ethyl radical produced in situ by decarbonylation of propionaldehyde is a crucial step in the process of preparation of irinotecan (4) (Scheme 16.6) [32], whereas the same kind of reaction led to the semisynthesis (Scheme 16.7) of gimatecan (9)[33], silatecan (10)[34], and belotecan (ll)[35j. This last compound entered clinical practice in Korea in 2005. 

Acetaldehyde behaves similarly in that CH3.CHOH is formed at higher concentrations of the aldehyde (Buley and Norman, 1964), but in this case and that of propionaldehyde other reactions also occur, and spectra of the protonated semiquinone radicals derived from biacetyl and bipropionyl, respectively, may be observed. It has been suggested that these arise as follows (Steven and Ward, 1965) ... 

One test of the latter hypothesis involves preparing a higher homologue, whose isomerization ought to yield characteristic products. To that end, the ditritiated w-propanol shown in Scheme 9 was synthesized and the neutral products from its /6-decay analyzed. Decay of the tritium at position 3 yields tritiated ethylene by cleavage of a carbon-carbon bond. Both propylene oxide and propionaldehyde are recovered as tritiated products from decay at position 2 in the presence of 0.5 bar trimethylamine, but no acetone is Protonated acetone would be expected among the thermal... 

The mechanism proposed by Schrauzer involves an activation process of the coenzyme in which the carbon-cobalt bond is broken. This is initiated by abstraction of a proton from C-4 of the coenzyme. We carried out an experiment to obtain evidence for such a proton abstraction. One would assume that if a proton were abstracted, it should become exchangeable with the solvent. We, therefore, carried out the conversion of propanediol to propionaldehyde in tritiated water (10). The experiment was carried out under conditions such that if 1% of the expected exchange had taken place, we should have detected it. However, we saw no tritium incorporation from the solvent into the coenzyme. Therefore, one must conclude that this experiment certainly does not support the proposed activation mechanism and is probably inconsistent with it. 

Most of the currently applied protocols for rhodium-catalyzed conjugate addition chemistry involve the use of aqueous solvent systems which ensure catalytic turnover by protonation of the intermediate rhodium enolate. Consequently, tandem reaction sequences with electrophiles other than a proton are troublesome. In early investigations, Hayashi reported a rhodium/BINAP-catalyzed conjugate addition-aldol reaction under anhydrous conditions by use of 9-aryl-9-borabicyclo[3.3.1]no nanes (9-Ar-9-BBN) as aryl sources [117]. The reaction between tert-butyl vinyl ketone (145) with 9-(4-fluorophenyl)-9-BBN (146) and propionaldehyde (147) led to the formation of a syn/anti-mixiuve of 148 in a 0.8 to 1 ratio (Scheme 8.39). 

If one of the aldehydes lacks a protons and possesses an unhindered carbonyl group, then a crossed aldol can be performed. As an example, consider what happens when a mixture of formaldehyde and propionaldehyde is treated with a base. 

In this case, only one major aldol product is produced. Why Formaldehyde has no a protons and therefore cannot form an enolate. As a result, only the enolate formed from propionaldehyde is present in solution. Under these conditions, there are only two possible products. The enolate can attack a molecule of propionaldehyde to produce a symmetrical aldol reaction, or the enolate can attack a molecule of formaldehyde to produce a crossed aldol reaction. The latter occurs more rapidly because the carbonyl group of formaldehyde is less hindered than the carbonyl group of propionaldehyde. As a result, one product predominates. 

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