1.4- dihydronicotinamides

The configuration of the amine was retained, except in the case of amino acid derivatives, which racemized at the stage of the pyridinium salt product. Control experiments showed that, while the starting amino acid was configurationally stable under the reaction conditions, the pyridinium salt readily underwent deuterium exchange at the rz-position in D2O. In another early example, optically active amino alcohol 73 and amino acetate 74 provided chiral 1,4-dihydronicotinamide precursors 75 and 76, respectively, upon reaction with Zincke salt 8 (Scheme 8.4.24). The 1,4-dihydro forms of 75 and 76 were used in studies on the asymmetric reduction of rz,>S-unsaturated iminium salts. 

The electrophilic character of sulfur dioxide does not only enable addition to reactive nucleophiles, but also to electrons forming sulfur dioxide radical anions which possess the requirements of a captodative" stabilization (equation 83). This electron transfer occurs electrochemically or chemically under Leuckart-Wallach conditions (formic acid/tertiary amine - , by reduction of sulfur dioxide with l-benzyl-1,4-dihydronicotinamide or with Rongalite The radical anion behaves as an efficient nucleophile and affords the generation of sulfones with alkyl halides " and Michael-acceptor olefins (equations 84 and 85). 

Although single-electron-transfer (SET) processes would be expected to be important in reactions that use metals as reagents, this type of process has also been recognized in the reduction of carbonyl groups that involve 1,4-dihydronicotinamide derivatives . Recent work by Oae and coworkers" has shown that an SET process is operative in the reduction of dibenzothiophene S-oxide by l-benzyl-l,4-dihydronicotinamide when the reaction is catalyzed by metalloporphins. The reaction is outlined in equation (18), but the study gave results of much more mechanistic than synthetic value. This type of study is relevant to understanding biochemical mechanisms since it is known that methionine sulphoxide is reduced to methionine by NADPH when the reaction is catalyzed by an enzyme isolated from certain yeasts . 

In a chemical model for oxidative phosphorylation77 the anaerobic oxidation of iV-benzyl 1,4-dihydronicotinamide by a pyridine solution of haemin was accompanied by the synthesis of ATP from ADP and inorganic phosphate. In support of an alternative chemical model involving sulphenyl phosphates as the reactive species,78 lipophilic thioureas have been shown to inhibit mitochondrial oxidative phos-... 

An intriguing use of a quaternary ammonium salt in a two-phase reaction is to be found with the regeneration of 1 -benzyl-1,4-dihydronicotinamide by sodium dithionite in a biomimetic reduction of thiones to thiols [12], The use of sodium dithionite in the presence of sodium carbonate for the 1,4-reduction of the pyri-dinium salts to 1,4-dihydropyridines is well established but, as both the dithionite and the pyridinium salts are soluble in water and the dihydropyridine and the thione are insoluble in the aqueous phase and totally soluble in the organic phase, it is difficult to identify the role of the quaternary ammonium salt in the reduction cycle. It is clear, however, that in the presence of benzyltriethylammonium chloride, the pyridine system is involved in as many as ten reduction cycles during the complete conversion of the thione into the thiol. In the absence of the catalyst, the thione is recovered quantitatively from the reaction mixture. As yet, the procedure does not appear to have any synthetic utility. 

These flavopapains (Fig. 19) were shown to be effective redox catalysts for the oxidation of hT-alkyl-l,4-dihydronicotinamides. The localization of the flavin moiety adjacent to the hydrophobic binding groove of the active site further allowed the constructs to exhibit substrate selectivity and, in some cases, saturation kinetics. The most effective flavopapain was the 8-isomer (FP-8) which reacted rapidly with a variety of M-alkyl-1,4-dihydronicotinamides. The best substrate was N-hexyl-l,4-dihydronicotinamide for which the of its... 

The presence of a base is also essential for the efficient reductive dehalogenation of RX by 1-benzyl-1,4-dihydronicotinamide (BNAH) via photoinduced electron transfer [121,122], Since the one-electron oxidation potential of the singlet excited state of BNAH ( BNAH ) is —3.1 V (vs. SCE) [50], which is more negative than the one-electron reduction potential of benzyl bromide (PhCH2Br), photoinduced electron transfer from BNAH to PhCH2Br occurs efficiently with the diffusion-limited rate [122]. This fast process needs no base catalyst to accelerate the electron transfer rate further. However, the photoinduced electron transfer results in... 

A different redox system model - the model for NADH - was also described by our group. [16] As electron transfer mediators, FMN and FAD accept two electrons from NAD(P)H and transfer one electron to metal centres in heme-containing proteins, nonheme iron, or molybdenum sites. However, the transfer of electrons between reduced pyridine - dinucleotide cofactors is slow under physiological conditions and must be catalysed by enzymes. Function of these enzymes was mimicked by a modification of the cofactor by a recognition site for its counterpart and, thus, efficient electron transfer was enabled directly. Functionalised 1,4-dihydronicotinamides bearing a recognition unit for flavins were synthesised (Scheme 18). 

The prepared compounds systematically differed in the distance of the dihydropyridine and the flavin recognition part. Binding between flavin and the NADH model systems was proved by potentiometric pH titrations. Redox reaction between the NADH model systems and flavin was monitored by UV - VIS spectroscopy. The intensity of the long-wave absorption of flavin at 456 nm significantly decreased during the reaction and the decrease was attributed to the reduction of flavin to the fully reduced flavohydroquinone. At the same time, the intensity of the peak around 360 nm decreased as well, because of the reduction of flavin and the concerted oxidation of the 1,4-dihydronicotinamide to the corresponding pyridinium species. Kinetics of the electron transfer was studied and two reasonable kinetic models were proposed. 

The reaction of 1 -benzyl- 1,4-dihydronicotinamide (BNAH) with a series of 1,1-di-para-substituted-phenyl-2,2-dinitroethylenes in oxygen-saturated acetonitrile produced various amounts of the corresponding ethanes and diaryl ketones depending on the electronic structure of the substituent groups, thereby indicating a spectrum of behaviour intermediate between polar and SET mechanisms (Scheme ll).261... 

The catalytic activity of the immobilized flavin was determined using the oxidation of an NADH-analog, namely 1-benzyl-1,4-dihydronicotinamide (BNAH), as a model reaction (Figure 8). If a potential of +0.9 V is applied to the system, hydrogen peroxide, which is formed in the aerobic oxidation of BNAH by flavin, can be oxidized... 

The remainder of this section is devoted to cases in which an immobilized oxidizing reagent can be regenerated by the action of a simple oxidant, such as a peroxide or O2. For instance, the flavin 10-ethyl-isoalloxazine was immobilized on organic polymers and used in the air oxidation of 1 -benzyl-1, 4-dihydronicotinamide (395). However, peracids, dioxiranes, and nitroxyl radicals are of much more synthetic importance. 

Figure 6. Modes of inclusion deduced for the 6-cyclodextrin complexes of (a) N-benzyl-1,4-dihydronicotinamide, (b) N-dodecyl-1,4-dihydronicotinamide, and (c) N-methyl-1,4-dihydronicotinamide (data adapted from reference [48]).

Shiragami, T. Fukami, S. Pac, C. Yanagida, S. Semiconductor photocatalysis Quantised CdS-catalysed photoformation of 1 -benzyl- 1,4-dihydronicotinamide (BNAH) from 1-benzylnicotinamide (BNA+), 7. Chem. Soc., Faraday Trans. 1993, 89, 1857. 

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