Nicotinic acid and

Trifluoromethylpyridine can be prepared ia 25—65% yield from nicotinic acid and sulfur tetrafluoride (434,439). An alternative method is the passage of chlorine iato a mixture of ( -picoline and hydrogen fluoride ia an autoclave (190°C, 3 MPa) (440). 4-Trifluoromethylpyridine is prepared ia 57% yield from isonicotinic acid and sulfur tetrafluoride. 

Key intermediates in the industrial preparation of both nicotinamide and nicotinic acid are alkyl pyridines (Fig. 1). 2-Meth5l-5-ethylpyridine (6) is prepared in ahquid-phase process from acetaldehyde. Also, a synthesis starting from ethylene has been reported. Alternatively, 3-methylpyridine (7) can be used as starting material for the synthesis of nicotinamide and nicotinic acid and it is derived industrially from acetaldehyde, formaldehyde (qv), and ammonia. Pyridine is the principal product from this route and 3-methylpyridine is obtained as a by-product. Despite this and largely due to the large amount of pyridine produced by this technology, the majority of the 3-methylpyridine feedstock is prepared in this fashion. 

Both nicotinic acid and nicotinamide have been assayed by chemical and biological methods. Owing to the fact that niacin is found in many different forms in nature, it is important to indicate the specific analyte in question. For example, if biological assay procedures are used, it is necessary to indicate whether the analysis is to determine the quantity of nicotinic acid or if niacin activity is the desired result of the analysis. If nicotinic acid is desired, then a method specific for nicotinic acid should be used. If quantitation of niacin activity is the desired outcome, then all compounds (bound and unbound) which behave like niacin will assay biologically for this substance (1). 

The Kixnig reaction (Fig. 5) has been used to determine the amount of nicotinic acid and niacinamide. In this procedure, quatemization of the pyridine nucleus by cyanogen bromide is followed by ring opening to generate the putative dialdehyde intermediate. Reaction of this compound with an appropriate base, such as p-rr ethyl am in oph en o1 sulfate (47) or sulfanilic acid (48), generates a dye. The concentration of this dye is deterrnined c olo rime trie ally. 

For more specific analysis, chromatographic methods have been developed. Using reverse-phase columns and uv detection, hplc methods have been appHed to the analysis of nicotinic acid and nicotinamide in biological fluids such as blood and urine and in foods such as coffee and meat. Derivatization techniques have also been employed to improve sensitivity (55). For example, the reaction of nicotinic amide with DCCI (AT-dicyclohexyl-0-methoxycoumarin-4-yl)methyl isourea to yield the fluorescent coumarin ester has been reported (56). After separation on a reversed-phase column, detection limits of 10 pmol for nicotinic acid have been reported (57). 

Owing to poor volatihty, derivatization of nicotinic acid and nicotinamide are important techniques in the gc analysis of these substances. For example, a gc procedure has been reported for nicotinamide using a flame ionisation detector at detection limits of - 0.2 fig (58). The nonvolatile amide was converted to the nitrile by reaction with heptafluorobutryic anhydride (56). For a related molecule, quinolinic acid, fmol detection limits were claimed for a gc procedure using either packed or capillary columns after derivatization to its hexafluoroisopropyl ester (58). 

Table 3. Nicotinic Acid and Nicotinamide (Vitamin B ) Content of Foodstuffs, mg/kg ...

Both nicotinic acid and nicotinamide have been used in the enrichment of bread, flour, and other grain-derived products. Animal feed is routinely supplemented with nicotinic acid and nicotinamide. Nicotinamide is also used in multivitamin preparations. Nicotinic acid is rarely used in this appHcation. The amide and carboxyHc acid have been used as a hrightener in electroplating baths and as stabili2er for pigmentation in cured meats. 

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). 

Bakers inactive dry yeast is also widely used in the food industry. This yeast may be grown specifically as a food supplement and consequently there is a choice in its composition by varying growth conditions and feedstock makeup. It can possibly produce high levels of nicotinic acid and thiamin, the cmde protein content can be raised to 50—55% and it can be used as a vehicle for the incorporation of micronutrients such as selenium or chromium into the diet. 

Phenothiazines, benzo-l,2,4-thiadiazine 1,1-oxides, fluoroquinolones, nicotinic acid, and nitrofuran derivative as potentially dangerous photosensitizers 98MI11. 

Niacin. Figure 1 Structure of nicotinic acid and nicotinamide. 

Nicotinic acid and related compounds react with l-chloro-2,4-dinitrobenzene in the manner of the cyanogen bromide reaction to yield derivative I, which possibly also decarboxylates at elevated temperature. In alkaline medium this derivative first adds an hydroxyl ion and then undergoes ring opening to yield the colored derivative II. 

The detection limits for nicotinic acid and nicotinamide are 200 ng substance per chromatogram zone. 

Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two compounds, nicotinic acid and nicotinamide, have the biologic activity of niacin its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation-reduction reactions (Figure 45-11). About 60 mg of tryptophan is equivalent to 1 mg of dietary niacin. The niacin content of foods is expressed as mg niacin equivalents = mg preformed niacin + 1/60 X mg tryptophan. Because most of the niacin in cereals is biologically unavailable, this is discounted. 

Figure 45-11. Niacin (nicotinic acid and nicotinamide) and nicotinamide adenine dinucieotide (NAD). Shows the site of phosphoryiation in NADP.

Nicotinic acid has been used to treat hyperlipidemia when of the order of 1—6 g/d are required, causing dilation of blood vessels and flushing, with skin irritation. Intakes of both nicotinic acid and nicotinamide in excess of 500 mg/d can cause liver damage. 

Hirschberg R, JC Ensign (1971a) Oxidation of nicotinic acid by a Bacillus species source of oxygen atoms for hydroxylation of nicotinic acid and 6-hydroxynicotinic acid. J Bacterial 108 757-759. 

Chapter 10 is devoted to the preparation and purification of hydrophilic vitamins (C, Bj, Bj, Bg, B[2, nicotinic acid and nicotinamide, pantothenic acid, biotin, and folic acid) in pharmaceutical preparations, food products, and biological samples. 

A TLC method was developed for the estimation of nieotinie aeid and nicotinamide (Fignre 10.7) in phatmacentical preparations containing other vitamins, enzymes, herbs, and drugs, etc. [16]. The percentage recoveries for nicotinic acid and nicotinamide were 100.1 + 1.9 and 100.2 1.5, respectively, with this system. Each alcohol extract of samples or standard was pnt on sihca gel TLC plates, which were developed with distilled water. Each silica gel spot visualized under UV lamp was collected and extracted with 0.1 mol/1 HCl. The optical density of each clear extract was measured at 262 run. 

FIGURE 10.7 Structural formula of nicotinic acid and nicotinamide. 1 — nicotinic acid, 2 — nicoinamide. 

Niacin should be instituted at the lowest dose and gradually titrated to a maximum dose of 2 grams daily for ER and SR products and no more than 5 grams daily for IR products. FDA-approved niacin products are preferred because of product consistency. Moreover, niacin products labeled as no flush don t contain nicotinic acid and therefore have no therapeutic role in the treatment of lipid disorders.28 The time until maximum effect on lipids for niacins is generally 3 to 5 weeks. 

Trigonelline is present in green coffee (1 %),15 but it is rapidly decomposed on roasting so that only about 0.1% trigonelline is present in a deeply roasted coffee.161 The products of trigonelline breakdown are evident in roasted coffee and include nicotinic acid and its methylester, pyridine, and p-picoline (Figure 17).3... 

The coordination modes found in Ni11 complexes with 2-(diphenylphosphino)nicotinic acid and its methyl ester and 2-(diphenylphosphino)benzoic acid and its methyl ester are surprising.696 The complex with the benzoic acid derivative shows the expected P,0 coordination with a six-membered chelate ring (252), while the nicotinic acid analogue forms a four-membered chelate ring with P,N binding (251). 

Nishiyama and Kuninori [65] described a combination method of assay for penicillamine using HPLC and postcolumn reaction with 6,6 -dithiodi(nicotinic acid). Thiols were separated by HPLC on a reversed-phase column (25 cm x 4.6 mm) packed with Fine Sil 08-10, with 33 mM KH2PO4 (adjusted to pH 2.2 with H3PO4) or 33 mM sodium phosphate (pH 6.8) as the mobile phase. Detection was by postcolumn derivatization with 6,6 -dithiodi(nicotinic acid), and measurement of the absorbance of the released 6-mercaptonicotinic acid was made at 344 nm. The detection limit for penicillamine was 0.1 nmol. A comparison was made with a... 

Walldius G, Wahlber G. Nicotinic acid and its derivates. In Lipoproteins in Health and Disease (Betteridge DJ, Illingworth DR, Shepherd J, Eds.). London Arnold 1999, 1181-1197. 

The vitamins niacin (nicotinic acid, and its amide niacin amide are... 

Nicotinic acid and related meta-carboxylic acids display the remarkable characteristic that coordination of the pendant carboxylic acid moieties to the Pt surface is controlled by electrode potential. Oxidative coordination of the carboxylate pendant occurs at positive electrode potentials, resulting in disappearance of the 0-H vibration and loss of surface acidity as judged by absence of reactivity towards KOH. Carboxylate in the 4-position of pyridine (as in INA) is virtually independent of electrode potential, whereas strong coordination of ortho-carboxylates to the Pt surface is present at most electrode potentials. Adsorbed pyridine carboxylic acids are stable in vacuum when returned to solution the adsorbed material displays the same chemical and electrochemical properties as prior to evacuation. 

Table II - Assignments of EELS Bands of Adsorbed Nicotinic Acid and Pyridine...

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