Nicotinic acid anhydride

Rinderknecht and Ma, requiring a quantity of nicotinic acid anhydride, noted that the known methods suffer from the extreme sensitivity of nicotinic acid chloride, and employed with success a method analogous to the mixed anhydride method of peptide synthesis. Equimolar amounts of nicotinic acid and triethylamine were dissolved in chloroform to produce a solution of the salt (1), and the solution was... 

The structure and absolute configuration of 7-0-nicotinoyl-strychnovo-line (66) were also established through semisynthesis. Treatment of strych-novoline (64) with nicotinic acid anhydride in the presence of 4-dimethylam-inopyridine gave 66, identical with the natural product (39). Similarly, when tetrahydrocantleyine (16) was treated with nicotinic anhydride, 7-O-nicotinoyl-tetrahydrocantleyine (67) was produced, identical with the natural product (39). 

Testosterone Nicotinate. I7-[(3-Pyridinylcarbon-yt)oxyJandrost-4-en-3-one testosterone 17-nicotinic acid ester Bolfortan. CjjHjtNOj mol wt 393.51. C 76.30%, H 7.94%, N 3.56%, O 12.20%, Prepared from testosterone and nicotinic acid anhydride Zirm, Weichsel, U.S. pat. 3,057,-856 (1962 to Lannacher Heilmittel). 

A 15.5%-soln. of 1 mole of phosgene in toluene added dropwise with stirring and ice-cooling to a soln. of 2 moles of nicotinic acid and 2 moles of dry triethylamine in dry alcohol-free chloroform, allowed to stand overnight at room temp. -> nicotinic acid anhydride. Y 92%. F. e. s. H. Rinderknecht and V.Ma, Helv. 47, 162 (1964). 

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). 

Nicotinic acid supplied by Matheson, Coleman and Bell yielded a colorless anhydride tr.s.P. grade material gave a slightly buff-colored product. 

Nicotinic acid, conversion to anhydride with phosgene and tnethylamine, 1,89... 

Pyridopyrimidine systems may also be accessed by in situ generation of pyridylisocyanates <2003TL2745>. Treatment of 2,3-pyridinccarboxylic anhydride with methanol leads to the formation of 2-(methoxycarbonyl)nicotinic acid that undergoes Curtius rearrangement on conversion to the 3-acyl azide with sodium azide and ethyl chloro-formate. Condensation of the resulting isocyanate with a series of amino acids leads to the synthesis of pyrido[3,2- T pyrimidines in good to excellent yield (Scheme 19). 

Reactions Of anhydrides. Treatment of 2,3-pyridinedicarboxylic anhydride with methanol leads to the formation of 2-(methoxycarbonyl)nicotinic acid <2003TL2745>. 

The conversion of 2,5-pyridinedicarboxylic acid Af oxide (284) inaceto-nitrile/acetic anhydride to the corresponding 6-amino-nicotinic acid (288) seems to be a Ritter reaction of intermediate cation 285 with acetonitrile, followed by rearrangement of intermediate 286 to 287, which is then saponified by potassium hydroxide to give 49% of 6-aminonicotinic acid (2M) and 8% of 6-hydroxynicotinic acid (289) (83EUP90I73). 

Reaction of phosgene with 1-amino nicotinic acid afforded the 3-azaisatoic anhydride (V). Treatment of (V) in DMF with propargylamine yielded the 1-aminonicotina-mide (VI). Phosgenation of (VI) in pyridine under reflux gave the expected product (VII) as depicted in scheme 216. 

Phosgene also has been used to lactonize an hydroxy acid (Wehrmeister and Robertson, 1968) and to convert a carboxylic acid to its anhydride (nicotinic acid to its anhydride) (Rinderknecht and... 

Nitrosyl chloride in iV,iV-dimethylfonnamide at low temperature has been used for the convenient deamination of adenosine, adenosine 5 -phosphate, adenosine 5 -triphosphate, and their iV -oxides to the corresponding inosine derivatives. Nitrous anhydride (N2O3) has been used to convert the coenzyme adenine-nicotinamide dinucleotide into hypo-xanthine-nicotinic acid dinucleotide. 

Tetrahydronaphthalene. See Tetrahydronaphthalene dl-Tetrahydronicotyrine. See Nicotine Tetrahydro-1,4-oxazine Tetrahydro-2H-1,4-oxazine Tetrahydro-4H-1,4-oxazine Tetrahydro-p-oxazine. See Morpholine Tetrahydrophthalic acid anhydride. See Tetrahydrophthalic anhydride... 

Nicotinic acid-1-oxide (X-222) on treatment with acetic anhydride is converted to 2-acetylnicotinic acid-l-oxide (X-223) and 3-carboxy- (X-224) and 5-carboxy-2-pyridone (X-22S). The structure of X-223 was proved by deriva-... 

A report of the synthesis of acid anhydrides using phosgene gas has also appeared in the literature [1040, 1041]. Nicotinic anhydride 1371 was prepared from nicotinic acid 1370 with phosgene in 87-93% yield, as described in a very detailed... 

Friedel-Crafts acylation also fails with pyridine l-oxide, but with nicotinic acid 1-oxide, acetic anhydride effects an interesting internal acylation, as well as the commoner nuclear hydroxylation Sa ( p 234)... 

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