Pyridone sodium salts

The salt is an ambient nucleophile and can undergo either N or 0 alkylation. Chung and Tieckelmann (17) have shown that unsubstituted pyridone sodium salts in acetonitrile or dimethylformamide solvent form primarily the N-alkylated product. Using 3-substituted... 

Direct use of pyridone sodium salts as fluorescent deriv atizing reagents. 

These reactions are useful because they run under mild conditions, use inexpensive or easily recoverable starting materials, and have short reaction times. The major problem in purification is the separation of the sodium pyridone sulfonate from excess sodium sulfite, sodium bromide, and sodium bromoalkyl sulfonate. However, these latter compounds usually would not interfere with the use of the pyridone sulfonate as a water tracer. From a practical point of view, the pyridone sulfonates need not be purified, but can be used directly. A modified synthetic procedure involves the treatment of the pyridone sodium salt with a tenfold excess of a,iu-dibromoalkane in acetonitrile, followed by removal of the excess dibromide by vacuum distillation. The resulting product is treated with an excess of sodium sulfite in aqueous ethanol. Evaporation of the solvent yields a useful tracer. Procedures given in the experimental section were... 

Phengl-2(lH)Pyridone-Propylsulfonate Sodium Salt Vllb. A solution of 3-phenyl-2(lH)pyridone sodium salt (0.264 g, 1.25 mmol) and 3-bromopropylsulfonate sodium salt (0.241 g, 1.25 mmol) in acetonitrile (650 mL) was brought to reflux with stirring for 24 h. The yield was 41%, as determined by HPLC. An analytical sample was obtained from the filtered residue of reaction by preparative HPLC. Anal. Calcd for Ci4Hi4NS04Na H2O C, 50.45 H, 4.8 N, 4.2. Found C, 50.38 ... 

The procedure for preparing 6-hydroxynicotinic acid is also based on a method described by von Pechmann. 6-Hydroxynico-tinic acid has also been prepared by decarboxylation of 6-hy-droxy-2,3-pyridinedicarboxylic acid by heating 6-hydra-zinonicotinic acid or its hydrazide with hydrochloric acid by the action of carbon dioxide on the sodium salt of a-pyridone at 180-200 and 20 atmospheres by heating the nitrile of 6-chlo-ronicotinic acid with alcoholic sodium hydroxide or hydrochloric acid from 6-aminonicotinic acid and by the prolonged action of concentrated ammonium hydroxide on methyl cou-malate. ... 

Pyridone Acid Chlorides as Fluorescent Derivatizing Reagents. A second derivatizing reagent, a fluorescent acid chloride, was synthesized from the sodium salt of 3-phenyl-2(lH)pyridone (IV). 

Figure 4. Chromatogram showing separation of the 3-phenyl-2(lH)pyridone alkylsulfonate sodium salts. Conditions as described in the text under "HPLC Separation Conditions."...

Pyridone IV was converted to its sodium salt by treatment with an equimolar amount of sodium methoxide in methanol (see procedure below under formation of the 3-phenyl-2(lH)pyridone sulfonates). The sodium salt was next treated with the methyl ester of a-bromo-p-toluic acid, obtained by treatment of the acid with BF3 etherate. 

General Procedures for the Synthesis of the Pyridone Sulfonates VIa,b,c and VIIa,b,c (25). A solution of 1.25 mmol of the sodium salt of 3-carbamoyl-2(lH)pyridone(III) or 3-phenyl-2(lH)pyridone and 1.25 mmol of the corresponding bromosulfonate sodium salt in 50 mL of acetonitrile was brought to reflux and stirred for 24 h. The reaction mixture was cooled and filtered through a sintered glass... 

Phenyl-2(lH)Pyridone Sodiim Salt. A solution of sodium metal (0.25 g, 11.3 mmol) and anhydrous methanol (10 mL) was allowed to react to form sodium methoxide. Pyridone IV (1.88 g, 11 mmol) was added to the solution and allowed to stand at room temperature for 24 h. The methanol was removed under reduced pressure and the residue was extracted with hot benzene 3 times and dried in the Abderhalden drying pistol for 30 min. The yield was 1.7 g (82%). 

Pyrano-fused heterocycles, namely pyrano[3,2-f]quinoline-2,5(6//)-diones, pyrano[3,2-f]benzopyran-2,5(6//)-dione, and pyrano[3,2-f]pyridine-2,5(67T)-diones, have been efficiently prepared by the condensation of 4-hydroxy-2-(l//)-quinolines, 4-hydroxycoumarin, or 4-hydroxy-(17/)-pyridone with a-acetyl-y-butyrolactone or the sodium salt of a-formyl-y-butyro-lactone in the presence of ammonium acetate <1999JHC467>. 

A similar procedure can be used for preparing other 2(l)-pyr-idones. For example, 3-cyano-6-isobutyl-2(l)-pyridone can be obtained from the sodium salt of formylmethyl isobutyl ketone, and 3-cyano-5,6-dimethyl-2(l)-pyridone can be prepared from the sodium salt of a-formylethyl methyl ketone.5... 

The procedure used for preparing the sodium salt of formyl-acetone is a modification of a previously described procedure.2 3-Cyano-6-methyl-2(l)-pyridone has been prepared by the condensation of /3-ethoxycrotonaldehyde diethyl acetal with cyano-acetamide 6 and by condensation of the sodium salt of formyl-acetone with cyanoacetamide.7... 

A whole class of iodanes with two iodine-nitrogen bonds comes from the reaction of [bis(trifluoroacetoxy)iodo]benzene with sodium salts of cyclic imides, such as phthalimide, saccharin and 2-pyridone (Scheme 22) [67]. Aliphatic analogs of imides failed to give isolable iodanes. 

Attempted alkylation of 2-pyridones often leads to mixtures of N- and O-alkylated products with the selectivity dependent on the reaction conditions. Alkylation of the sodium salt of 2-pyridone often leads to iV-alkylation while alkylation of the silver salt results in O-alkylation. For example, /3-D-galactopyranose pentaacetate reacts with silver 2-pyridoxide in toluene under reflux to give the pyridylgalactopyranoside 100 in good yield (Equation 67) <2001T3267>. 

The i-methyl-2-pyridone is salted out of the reaction mixture by the addition of 400-500 g. of anhydrous sodium carbonate to the well-stirred solution. When no more of the sodium carbonate dissolves, the stirring is discontinued and the yellow or brown oily layer containing most of the desired pyridone, together with some of the unreacted pyridinium salt, water, and inorganic salts, is separated from the aqueous mixture. The aqueous mixture is filtered (Note 2) to remove the excess sodium carbonate and the precipitated potassium or sodium ferrocyanide. The filtrate is divided into three portions, each of which is extracted twice with 200-cc. portions of technical iso-amyl alcohol (Note 3). The alcohol used for the second extraction of the first aqueous portion is satisfactory for the first extraction of a second aqueous portion, et cetera, so that a total volume of 800 cc. is used. The iso-amyl alcohol extracts are combined and added to the oily layer which was first separated from the reaction mixture. An aqueous layer usually appears and is separated and extracted with another 100-cc. portion of amyl alcohol. 

The extraction of the pyridone from the aqueous solution is difficult when benzene or ether is used as a solvent. i-Methyl-2-pyridone, when dry, is very soluble in ethyl ether, benzene, and most organic solvents. It is, however, practically insoluble in petroleum ether or ligroin. When a mixture of water, benzene, and a little pyridone is shaken together all the pyridone is found in the water layer. When the pyridone is salted out from water by adding a sufficient quantity of potassium carbonate, the oily layer does not dissolve when benzene or ethyl ether is added, but three layers are formed. The pyridone seems to be extracted by ether or benzene only when the aqueous solution is strongly saturated with sodium hydroxide or potassium hydroxide and then the tendency to form an emulsion is so great that separation of the layers is extremely difficult. 

An additional element of complication in preparing the allyl ethers utilizing the salts of hydroxypyridines lies in the intervention of SN2 displacements. Thus the sodium salt of 2-pyridone on treatment with crotyl chloride or with 3-chloro-1 -butene afforded the same compound, viz., l-crotyl-2-pyridone5 [Eq. (1)]. 

Pyridines. A pyridinol (2,3,5-trichloro-4-pyridinol) known as Dax-tron and a pyridone (the sodium salt of 3-carboxyl-l-(p-chlorophenyl)-4,6-dimethyl-2-pyridone) known by the designation RH-531, both showed activity in screening tests. Neither of these pyridines has been carried to an advanced stage. 

The second route to ipalbidine also provides the first synthesis of its /5-d-glucoside ipalbine.3 2-Methoxypyrroline (4) was condensed with methyl acetoacetate at 85 °C in the absence of solvent to give the keto-ester (5). Acylation of the sodium salt of (5) was achieved with p-methoxyphenylacetyl chloride, but the expected acyl derivative could not be isolated. However, after the addition of a further equivalent of sodium hydride and heating at 80 °C the cyclization product (6) was obtained in moderately good yield. Some of the corresponding carboxylic acid was also isolated. Demethylation and decarboxylation of (6) by means of 48 % hydrobromic acid then gave the tetrasubstituted pyridone (7), which was... 

Alkylation of the sodium salt of 2-pyridone with chloromethyltrimethylsilane allows subsequent introduction of further groups on to the nitrogen substituent. " ... 

The gas-phase equilibrium between 2-hydroxypyridine and 2-pyridone favours the hydroxy-form, but in the equilibrium between 2-hydroxypyridine iV-oxide and N-hydroxy-2-pyridone, the major tautomer is the hydroxy-pyridone. Bicyclic adducts between 2-pyridones and dimethyl acetylene-dicarboxylate, unobtainable at atmospheric pressure, have been obtained at 10—15 kbar. A novel route to iV-hydroxy-2-pyridone involves the trimethyl-silylation of 2-pyridone followed by oxidation of the resulting 2-(trimethyl-silyloxy)pyridine with the DMF complex of molybdenum pentoxide. p-Nitro-phenols (45) and nitro-acetamides (46) are formed from the reaction of 3,5-dinitro-2-pyridones (43) with the sodium salts of /3-keto-esters (44) (Scheme 20). ... 

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