Nicotinamide, 1 - -1,4-dihydro reductions

It was shown that dibenzothiophene oxide 17 is inert to 1-benzyl-l,4-dihydro nicotinamide (BNAH) but that, in the presence of catalytic amounts of metalloporphyrin, 17 is reduced quantitatively by BNAH. From experimental results with different catalysts [meso-tetraphenylporphinato iron(III) chloride (TPPFeCl) being the best] and a series of substituted sulfoxides, Oae and coworkers80 suggest an initial SET from BNAH to Fe1 followed by a second SET from the catalyst to the sulfoxide. The results are also consistent with an initial coordination of the substrate to Fem, thus weakening the sulfur-oxygen bond in a way reminiscent of the reduction of sulfoxides with sodium borohydride in the presence of catalytic amounts of cobalt chloride81. 

The electrochemistry of N-substituted nicotinamides (101) dominates the reports on ring-substituted pyridinium ions. There is also some controversy about the products of reduction. Elving et al. have reviewed this area up to about 1975.158 Apparently there is little doubt that a dihydro product, either 102 or 103, and dimer, either 104 or 105, are formed (Scheme 36). The latest... 

Cyanide ions attack the 4-position in pyridinium salts. For example, nicotinamide pyr-iV-methiodide (143, R = CHS) and di-phosphopyridine nucleotide give the 4-cyano- 1,4-dihydro derivatives (144) 328,329 3-Acetyl-iV-benzylpyridinium chloride similarly gives the 4-cyano-1,4-dihydro derivative and no attack at C-2 has been reported.330 Hydrosulfite reduction of nicotinamide quaternary salts... 

It must, nonetheless, be emphasized that the products of reduction of pyrimidine have not been unequivocally identified, largely due to their instability in the presence of air (oxygen). Furthermore, the UV absorption spectra of the reduction products of waves I and II (kmax284 nm, smax 1.5 x 103) are suggestive of rapid conversion (proton-catalyzed hydration ) of the products, since both the dimer and the dihydro derivative possess a reduced system of aromatic bonds relative to the parent pyrimidine, as a result of which the UV absorption maximum should be shifted to the violet, whereas it is, in fact, shifted 44 nm to the red (from 240 nm to 284 nm) for both products. Of possible relevance to this is the fact that the reduced rings of 4-aminopyrimidine 102) and nicotinamide 103) undergo acidic hydration to form products absorbing at 280 to 290 nm. 

Sodium cyanoborohydride (10) produces mainly 1,4-dihydropyridines (11) in the reduction of 3,5-di-cyano- and 3,5-diethoxycarbonyl-pyridines, diborane produces more of the 1,2-isomer. With NBH, mixtures of 1,2- and 1,4-dihydro adducts are produced, the latter predominating when carried out in pyridine solution. Nicotinamide (13) in ethanol can be reduced to (8) in moderate yield at 140 C in diglyme the tetrahydropyridine (8) was isolated in admixture with the piperidine (14), presumably via dehydration of the amide. 3-Nitropyridine affords 3-nitropiperidine in moderate yield when reduced in ethanol. The carboxylic acid and halo derivatives of pyridine are generally not reactive toward NBH. 

A novel electron transfer free radical mechanism has been elucidated for sodium naphthalenide induced demercuration. A new reductant for the cleavage of the C—Hg bond, A -benzyl-1,4-dihydro-nicotinamide (BNAH), has also been proposed it reduces alkylmercury(II) acetates via an electron transfer chain substitution mechanism. ... 

Free forms of the vitamin are white, stable solids that are quite soluble in water. The oxidized coenzymes are labile to alkali, whereas the reduced (dihydro) coenzymes are labile to acid. Reduction of the oxidized coenzymes commonly occurs by addition of a hydride ion to the para (4) position of the nicotinamide ring, with simultaneous formation of a solvated proton. NADH and NADPH (but not NAD and NADP) absorb light in the near ultraviolet region (339 nm). This forms the basis for many biochemical assays. 

The chemically redox reactive part of the coenzyme is the nicotinamide residue. The formal addition of hydride to the pyridinium ring gives 1,4-dihydronicotina-mide, NADH, selectively in biological systems although the 1,2- and 1,6-dihydro isomers are also formed by simple chemical reduction. Hydride-ion transfer takes place directly between the nicotinamide system and the substrate, as shown by... 

It was revealed that the optical yield did not depend on the reaction period, in contrast with the case in monomeric 1, 4-dihydro-nicotinamide where the oxdized form produced in the course of the reduction was thought to participate in the complex. This indicates that the intramolecular interaction between 1,4-dihydronicotinamide moieties with the aid of Mg(II) is stronger than the intermolecular interaction between the reduced and oxidized forms. 

Oishi T, Akita H 0983) Asymmetric reduction by yeasts. Formation of optically active synthons having two chiral centers useful for natural product synthesis. J Synth Org Chem Jpn 41 1031-1043 Okamoto T, Ohno A, Oka S (1977a) Reaction of N-propyl-1,4-dihydro-nicotinamide with ferricyanide ion. J Chem Soc Chem Commun 181-182 Okamoto T, Ohno A, Oka S (1977b) Alkali-metal ion acceleration of the electron-transfer reaction between N-propyl-1,4-dihydronicotinamide and ferricyanide ion. J Chem Soc Chem Commun 784-785 Okamoto T, Ohno A, Oka S (1979) Reduction of transition-metal salts by N-propyl-1,4-dihydronicotinamide. Bull Chem Soc Jpn 52 3745-3746 Ono N, Tamura R, Kaji A (1980) 1-Benzyl-1,4-dihydronicotinamide as a reagent for replacing aliphatic nitro groups by hydrogen An... 

The direct reduction of glutamate 5-phosphate (Scheme 12.3) with the nicotinamide adenine diphosphate (NADPH)/NADP+-dependent glutamate-5-semialde-hyde dehydrogenase (EC 1.2.1.41) as shown in Scheme 12.5 produces glutamate 5-semialdehyde. The aldehyde spontaneously undergoes cyclization to (5)-3,4-dihydro-2//-pyrrole-2-carboxylate, which is then reduced to L-proline (Pro, P).The reduction is accomplished again with the phosphorylated nicotinamide adenine dinucleotide being oxidized while in the presence of the enzyme pyrroline-5-car-boxylate reductase (EC 1.5.1.2). 

The de terated coenzyme, DPND, formed from DPN and MeCD20H in the presence of enzyme, transfers all its deuterium to Me.GHO on enzymatic reoxidation, whereas DPND formed from D2O and dithionite transfers only half of its deuterium in this process the enzymatic reduction is stereospecific but the dithionite reduction is not 3. Quaternization and Decker oxidation of nicotinamide obtained from DPND, formed by both enzymatic and dithionite reduction of DPN, gave 3-carboxamido-l-methyl-2- and -6-pyridone, both of which were still labelled (the enzymatic product half as much as the dithionite product). Thus, the quaternary nicotinamide nucleus of DPN is converted into the 1,4-dihydro form both by enzymatic and dithionite reductioni084 xhe same point was also proved for various quaternary derivatives of nicotinamide and for DPN by observing that the product of dithionite/D20 reduction could enzymatically transfer deuterium to an acceptor, whilst quaternary salts synthesized with deuterium at C(2) or G(6), and then reduced with dithionite/H20, could notions. 

The 1,4-dihydro structure of the dithionite reduction product of nicotinamide methochloride has been conclusively demonstrated by these methods ose and by nuclear magnetic resonance spectroscopyio , xhe last technique has also been used to demonstrate the 1,4-dihydro structure of the product from 3,5-di-ethoxycarbonyM,2,6-trimethylpyridinium and di-... 

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