Nicotinic acid amination

Oxidation. The synthesis of quinolinic acid and its subsequent decarboxylation to nicotinic acid [59-67-6] (7) has been accompHshed direcdy in 79% yield using a nitric—sulfuric acid mixture above 220°C (25). A wide variety of oxidants have been used in the preparation of quinoline N-oxide. This substrate has proved to be useful in the preparation of 2-chloroquinoline [612-62-4] and 4-chloroquinoline [611 -35-8] using sulfuryl chloride (26). The oxidized nitrogen is readily reduced with DMSO (27) (see Amine oxides). 

Nicotinyl alcohol (3-pyridinylcarbinol, 3-pyridinemethanol) (27) has use as an antilipemic and peripheral vasodilator. It is available from either the reductions of nicotinic acid esters or preferably, the reduction of the nitrile to the amine followed by dia2otation and nucleophilic displacement. It is frequently adininistered in the form of the tartrate (Eig. 7). Nicotinic acid is frequently used as a salt in conjunction with basic dmgs such as the peripheral vasodilator xanthinol niacinate (28). Nicotinic acid and its derivatives have widespread use as antihyperlipidemic agents and peripheral vasodilators (1). 

The coupling of o-aroylbenzoic or nicotinic acids with phosphorylated amines using dicyclohexylcarbodiimide (DCC)/4-dimethylaminopyridine (DMAP) followed by deprotonation with potassium bis(trimethylsilylamide) and cyclization gave isoquinolines or naphthyridinones in good yields (Scheme 43) <1996T4433>. 

Several protocols using multi-component reactions to prepare multisubstituted furans were reported. One procedure was that using acetylenedicarboxylate, isocyanides, triphenylphosphine and an aromatic carboxylic acid <07SL1610>. The others include the reaction of acetylenedicarboxylate, isocyanides and nicotinic acid <07S2637>, of dibenzoylacetylene, amines and diketene <07T8083>, of alkyl isocyanides, aromatic aldehydes and 3-cyanoacetyl indoles <07TL8987>, and of naphthoquinone, isocyanides and aldehydes <07T10269>. 

Exchange of the nicotinamide moiety of NADP for nicotinic acid, forming NAADP. Early studies also showed that the enzyme can catalyze exchange of nicotinamide with a variety of other bases, including histamine. Formation of histamine adenine dinucleotide phosphate was thought to provide an alternative to amine oxidase for rapid inactivation of histamine. 

Azaperone, brompheniramine, chlorphenir amine, isoniazid, metyrapone, nicametate, nicotinamide, nicotine, nicotinic acid, nifenazone, nikethamide, pheniramine, xanthinol nicotinate... 

The majority of alkaloids have been found to be derived from amino acids, such as tyrosine, phenylalanine, anthranilic acid, tryptophan/tryptamine, ornithine/arginine, lysine, histidine and nicotinic acid (Fig. 2.1). However, alkaloids maybe derived from other precursors such as purines in case of caffeine, terpenoids, which become aminated after the main skeleton has been synthesized i.e. aconitine or the steroidal alkaloids, are found in the Solanaceae and Liliaceae. Alkaloids may also be formed from acetate-derived polyketides, where the amino nitrogen is introduced as in the hemlock alkaloid, coniine. 

Glycosides of this vitamin (sometimes denoted as vitamin B3) were not described, however, there exists an evidence that bound niacin from wheat bran (termed niac)4in) has a single nicotinic acid moiety at least partially linked to an aromatic amine with glucose, xylose, and arabinose in a 6 3 1 molar ratio per molecule, with approximately three cinnamic acid esters [152,177,178]. It seems that these glycosidic complexes limit the bioavailability of the nicotinamide and for its liberation they must be treated, e. g., by soaking com in a lime solution, traditionally performed in Central America during production of tortillas [179]. 

Good use is made of this chemistry in the synthesis of nifluminic acid 69, an analgesic with a pyridine ring. Disconnection of the C—N bond suggests a 2-chloropyridine 70 starting material easily derived from nicotinic acid 60 and a simple aromatic amine 72 available by functionalisation of trifluorobenzene 74. 69 Is actually available as niflumic acid from Aldrich. 

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