Isonicotinamide

Nicotinamide [98-92-0] (26) and isonicotinamide [1453-82-3] (32) undergo Hofmann rearrangements to form 3- (33) and 4-aminopyridine (34), respectively (35). This provides an important route for the manufacture of these amines. 

Dopamine, a neurotransmitter, was covalently coupled, via an amide bond, to a modified polystyrene having A-(2-(3,4-dihydroxyphenyl)ethyl) isonicotinamide units. The dopamine-coupled polymer was coated onto glassy carbon electrodes. In aqueous electrolyte solutions (pH 7), cathodic current caused cleavage of the amide linkage and release of dopamine at potentials more negative than 0.9 V [41]. The chemical scheme for the amide bond cleavage is presented in Figure 18. 

An attempt to demonstrate the direct outer-sphere reduction of HOC1 was recently published, in which the reductant was selected to be [Ru(NH3)5isn]2+ because of its well-known behavior as an outer-sphere reductant and its relatively low standard potential (10). In this reagent the ligand isn is isonicotinamide. Further efforts to promote reaction via HOC1 entailed the use of chloride-free preparations of HOC1. 

The surface-enhanced Raman spectra (SERS) provide information about the extent of protonation of the species adsorbed at the silver/aqueous solution interface. The compounds investigated were 4-pyridyl-carbinol (1), 4-acetylpyridine (2), 3-pyridine-carboxaldehyde (3), isonicotinic acid (4), isonicotinamide (5), 4-benzoylpyridine (6), 4-(aminomethyl)pyridine (7) and 4-aminopyridine (8). For 1, the fraction of the adsorbed species which was protonated at -0.20 V vs. SCE varied with pH in a manner indicating stronger adsorption of the neutral than the cationic form. The fraction protonated increased at more negative potentials. Similar results were obtained with 3. For all compounds but 4, bands due to the unprotonated species near 1600 cm-1 and for the ring-protonated species near 1640 cm-1 were seen in the SERS spectra. 

Isonicotinamide, 5. This compound was sufficiently soluble to allow SERS spectra to be obtained at the 50 mM level in 0.10 M KC1 and 0.10 M KC1 + 0.10 M HC1 at -0.20 V. The spectra resembled those seen with other pyridines. In particular, an intense band at 1600 cm-1 was seen with the neutral electrolyte and it was replaced by a band at 1640 cm-1 in the acidic electrolyte. Of the two basic sites, only the ring nitrogen will be protonated in 0.10 M HC1 (22) so, with this compound also, the 1640 cm-1 band appears to be due to the protonated pyridine. No carbonyl band was seen in either spectrum. 

Pyridylcarbinol, 4-acetylpyridine, 3-pyridine-carboxaldehyde and 4-aminomethylpyridine were obtained from Aldrich Chemical Company (Milwaukee, Wisconsin) and were purified by distillation at reduced pressure. 4-Benzoylpyridine was recrystallized from ethanol. 4-Aminopyridine (G. Frederick Smith Chemical Company), isonicotinic acid (Aldrich) and isonicotinamide (Aldrich) were used as received. Triply distilled water was used. All other reagents were analytical reagent grade. 

Chiang and Lin also irradiated alcoholic solutions of isoniazid, but used a high-pressure mercury lamp. From the methanol solution they isolated small yields of isonicotinic acid, isonicotinamide, the hydrazone (263) and the bishydrazide (265). From the ethanolic solution, they obtained isonicotinamide, the hydrazone (262) and the bishydrazide (265). As before, (262) was assumed to arise via photo-oxidation of the solvent. The other products were explained as resulting from either CO-N or N-N bond homolysis [163]. 

In order to obtain further information on the magnitude of the overall reaction volume and the location of the transition state along the reaction coordinate, a series of intermolecular electron-transfer reactions of cytochrome c with pentaammineruthenium complexes were studied, where the sixth ligand on the ruthenium complex was selected in such a way that the overall driving force was low enough so that the reaction kinetics could be studied in both directions (153, 154). The selected substituents were isonicotinamide (isn), 4-ethylpyr-idine (etpy), pyridine (py), and 3,5-lutidine (lut). The overall reaction can be formulated as... 

The rate law for the oxidation of [Ru(NH3)5(FlL)] + (HE = isonicotinamide) by I2 in acidic solution contains two terms, one depending on P2] and one depending on [I3 ] and [Ru complex]. An outer-sphere electron-transfer mechanism is proposed for each term. Reduction of [Ru (NFl3)5L] + (TIL = nicotinamide or isonicotinamide) to [Ru (NH3)5L]+ is accompanied by an isomerization from the amide-bonded L to pyridine-bonded FIL. Bromine oxidation of... 

Figure 10.1 Inhibitors and activators of sirtuins. Inhibitors. 1, sirtinol 2, splitomicin 3, cambinol 4, H R-73 5, EX-527 6, AGK-2 7, tenovin-6 8, nicotinamide. Activators 9, resveratrol 10, SRT-1720 11, isonicotinamide.

In addition to resveratrol and other compounds that activate SIRTl by promoting peptide binding, a different mechanism has been described for isonicotinamide (11), which was shown to activate yeast Sir2 through relief of nicotinamide inhibition [45 ]. 

Isomer shift data, Fe,S4 clusters, 38 20, 50 Isomorphic substitution, 39 179, 186 p-Isonicotinamide complexes, osmium, 37 307 p-lsonicotinamidepoly(proline) complexes, osmium, 37 307 Isonitrile complexes osmium, 37 245 technetium(I), 41 13-14 technetium(II), 41 31 technetium(IIl), 41 45 Isopolymolybdates, 19 239ff 19 265-280 crystallization from aqueous solution, 19 265-269... 

Electrochemical and subtractively normalized interfacial FTIR studies of 4-cyanopyridine adsorption on Au(lll) electrode [245] have shown that this compound is totally desorbed at potentials lower than —0.7 V versus SCE. At less negative potentials, the molecules were flatly oriented n bonded) on the surface and reoriented to the vertical position, when potential approached OV. At potentials higher than 0.05 V, adsorption of 4-cyanopyridine becomes dissociative and the compound is partially hydrolyzed to isonicotinamide. 

In another early experiment, the participation of N,N-diethyl isonicotinamide 444 in a tandem metalation sequence to give azathioquinone 446 was demonstrated (Scheme 133) (80JA1457). Thus, a sequence of metalation (sec-BuLi/TMEDA), condensation with 3-thiophene carboxal-dehyde, metalation under the same conditions, and warming to room temperature furnished the quinone 446 in 20% yield, presumably via 2-thiophene DoM reaction of the intermediate 445. 

In a sequence that proceeds by tandem directed ortho metalation steps (Scheme 133) the N,N-diethyl isonicotinamide (447a) has been converted into the chemotherapeutic alkaloid ellipticine (589) (Scheme 182) (80JA1457). Thus, in a rapid, one-pot procedure, metalation of 447a followed by condensation with N-protected indole-3-carboxaldehyde derivatives leads to the intermediates 615 which, upon second metalation and aerial oxidation affords the quinones 616 in modest to good yields. Established steps were used to convert 616, R = CH2OMe into ellipticine (589), concluding a route which complements that based on the oxazolino DMG (Scheme 175). 

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