Nicotinic acid, substituted

P-Picoline may serve as an important source of nicotinic acid [59-67-6] for dietary supplements. A variety of substituted pyridines may be prepared from acrolein (75—83). 

Tobacco Alkaloids. The relatively small number of alkaloids derived from nicotinic acid (27) (the tobacco alkaloids) are obtained from plants of significant commercial value and have been extensively studied. They are distinguished from the bases derived from ornithine (23) and, in particular, lysine (24), since the six-membered aromatic substituted pyridine nucleus common to these bases apparendy is not derived from (24). 

Using the pK values of the 5-substituted picolinic acids (5-R-2-COOH) and the 6-substituted nicotinic acids (6-R-3-COOH), in 50% ethanol at 25°, considerably better correlations are observed, with p = 3.31 and 1.60, respectively. The transmission through the... 

Condensation of ethyl acetoacetate with phenyl hydrazine gives the pyrazolone, 58. Methylation by means of methyl iodide affords the prototype of this series, antipyrine (59). Reaction of that compound with nitrous acid gives the product of substitution at the only available position, the nitroso derivative (60) reduction affords another antiinflammatory agent, aminopyrine (61). Reductive alkylation of 61 with acetone in the presence of hydrogen and platinum gives isopyrine (62). Acylation of 61 with the acid chloride from nicotinic acid affords nifenazone (63). Acylation of 61 with 2-chloropropionyl chloride gives the amide, 64 displacement of the halogen with dimethylamine leads to aminopropylon (65). ... 

Beta nicotinic acid to 6-hydroxy nicotinic acid 3-substituted pyridine to a building block for imidacloprid (an insecticide) R-Cyanohydrins from benzaldehydes and HCN ... 

Nicotinic acid amide p-Substituted acetoacetanilides 5-Nitrosalicylate... 

More powerful directing groups such as those based on amides and sulphonamides are successful with pyridines as with carboxylic rings, and will not be discussed separately. The enhanced acidity of pyridine ring protons makes the simple carboxylate substituent an ideal director of lithiation in pyridine systems . The pyridinecarboxylic acids 232-234 are deprotonated with BuLi and then lithiated with an excess of LiTMP all the substitution patterns are lithiated nicotinic acid 233 is lithiated in the 4-position (Scheme 113). The method provides a valuable way of introducing substituents into the picolinic, nicotinic and isonicotinic acid series. 

Sustained-release Do not substitute sustained-release (modified-release, timed-release) nicotinic acid preparations for equivalent doses of immediate-release (crystalline) nicotinic acid. 

Hepatic Nicotinic acid hepatotoxicity (including cholestatic jaundice) has occurred. Cases of severe hepatic toxicity, including fulminant hepatic necrosis, have occurred in patients who have substituted sustained-release nicotinic acid products for immediate-release nicotinic acid at equivalent doses. Monitor ALT prior to treatment, every 6 to 12 weeks during the first year, and periodically thereafter (approximately 6-month intervals). 

A number of syntheses of substituted 2,3 -bipyridines are worthy of note. Tetracyclone heated at 215°C with nicotinonitrile affords 3,4,5,6-tetraphenyl-2,3 -bipyridine, whereas 3,4-di(2-pyridyl)pyridine is obtained by an oxidative degradation of the corresponding 6,7-disubstituted thiazolo[3,2-a]-pyridinium salt. Nicotinic acid on UV irradiation in aqueous solution at pH 4-6 gives 2,3 -bipyridine-5-carboxylic acid, whereas irradiation of picolinic acid in the same pH range in the absence of metal ions gives some 2,3 -bipyridine. 6,6 -Diphenyl-2,3 -bipyridine is thought to be formed from... 

Substituted nicotinic acid derivatives are useful in the synthesis of pesticides and pharmaceuticals as specific inhibitors of NAD and/or NADP dependent enzymes. 6-Hydroxynicotinic acid is a very useful intermediate in the synthesis of such inhibitors. 

The chemical synthesis of 6-substituted nicotinic acids is difficult and together with the... 

Furo[3,4-r]pyridine derivatives are generated from the reaction of 2,3-dihalopropenyl ketones with the ethyl ester of / -aminocrotonic acid. Initial reaction products are substituted nicotinic acids which can be partially converted into the furopyridines under harsh vacuum distillation conditions (Scheme 12) <2005CHE1009>. 

A synthesis of pyrrolo[2,3-, ]pyridine derivatives from nicotinic acid or 2,6-dichloropyridine affords 1,3- and 1,3,6-substituted pyrrolo[2,3-, ]pyridines <2006JOC5538>. 

Pharmaceutically important 3-substituted-[l,8]naphthyridine-2,4-diones have been prepared by the reaction of 2-methyl-477-pyrido[2,3-r/][3,l]oxazin-4-one with active methylene compounds (Scheme 66) <1997J(P1)1487, 2003JOC4567> and by the same group via an intramolecular azadiene-ketene electrocyclization reaction of amino-nicotinic acid derivatives in a related process <2001JOC4413>. 

China Heracleum dissectum Ledeb. This herb is used in the same way and as a substitute for Angelica (ferulic acid, succinic acid, nicotinic acid, uracil, adenine, butylidenephalide, ligustilide, folinic acid, biotin, polysaccharide33), with less effect.60 Relieve headache, toothache, hematuria, gonorrhea, itching skin, swellings, remove corns from the feet. 

Sherlock, M. H. and Sperber, N. (Schering Corp.) Substituted nicotinic acids and method for the manufacture thereof, US 3 337 570,1967... 

Niacm - piTAMINS - NIACINE,NICOTINAMIDEAND NICOTINIC ACID] (Vol 25) - [FEEDS AND FEED ADDITIVES - PET FOODS] (Vol 10) - [FINECHEMICALS - PRODUCTION] (Vol 10) - [FEEDS AND FEED ADDITIVES - RUMINANT FEEDS] (Vol 10) -m dairy substitutes pAIRY SUBSTITUTES] (Vol 7) -m dairy substitutes pAIRY SUBSTITUTES] (Vol 7) -deficiency of piTAMINS - NIACINE,NICOTINAMIDEAND NICOTINIC ACID] (Vol 25) -dietary requirements piTAMINS - NIACINE, NICOTINAMIDE AND NICOTINIC ACID] (Vol 25) -m nuts PUTS] (Vol 17) -m nuts PUTS] (Vol 17)... 

An iron-catalyzed reaction of an a,P-unsaturated oxime such as 68 with a P-oxo ester also gave pyridine derivatives such as nicotinic acid 69 [99]. Under the reaction conditions (150-160 °C, without solvent) first Michael adducts such as intermediate 70 are presumably formed, which further condense via intermediate 71. This method is not restricted to a centric symmetry in the substitution pattern, which is an advantage compared with the Hantzsch synthesis. Moreover, the method starts with hydroxylamine being two oxidation stages above ammonia therefore, no oxidation in the final stage from dihydro- to pyridine is necessary (Scheme 8.31). 

Lithiation of 5-bromonicotinic acid protected as a secondary or tertiary amide and also (4,4/-dimethyl)oxazoline (11) with lithium amides has been reported.62 The unusual C(2) and C(4) regioselective lithiation of 3-bromo-5-(4,4,-dimethyl)oxazolin-ylpyridine using LTMP versus LDA has been observed, providing a new route to substituted nicotinic acid scaffolds. 

E. coli K12 343/113 contains three markers that are detected by reverse mutation reversion to arginine independence, reversion to nicotinic acid independence, and reversion to the ability to ferment galactose.289 The arg site seems to be more sensitive to chemicals that cause base-pair substitution mutation, whereas the gal and nad sites appear to be more sensitive to chemicals that cause frameshift mutation. 

The same activation that allowed simple electrophilic substitution—oxidation to the N-oxide— can also allow a useful nucleophilic substitution. The positive nitrogen atom encourages nucleophilic attack and the oxygen atom can be turned into a leaving group with PCI3. Our example is nicotinic acid whose biological importance we will discuss in Chapter 50. 

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