3- Amino-4-hydroxypyridine, reaction with

Chlorination of the pyridone (436 R = 4-pyridinyl) with phosphorus oxychloride followed by a reaction with hydrazine gave a low yield of the corresponding 2-amino-3-hydroxypyridine (437). Cyclization of this product was carried out by a reaction with l,r-carbonyldiimidazole in DMF at room temperature to give the oxazolo[4,5-6]pyridine (438 R = 4-pyridinyl) (Scheme 51) <94JMC248>. 

In other reactions, attack on the pyridine nitrogen atom is made by the electrophilic )S-carbon atom of an a,j8-unsaturated carbonyl compound. An example is the formation of (61) from pyridine and maleic acid other unsaturated acids behave similarly, but the reaction is not completely general2 2,352,462 In some circumstances, cyclization follows the initial reaction, as in the formation of (62) and (63) from 2-hydroxy- and 2-amino-pyridine, respectively, with a-bromacrylic acid . The similarly activated acrylonitrile reacts with 2-hydroxypyridine, giving l-]8-cyanoethylpyrid-2-onei7i 464. 

Reaction of equimolar amounts of 3-amino-2-hydroxypyridine (78) with 3 produced 2-(2-aminopyrido-[2,3-f ]-l,4-oxazine-3-ylidene)indan-l,3-di-one (125) (Scheme 39,05ZDN(B)999). 

The reaction of furans with ammonia and its derivatives is of considerable synthetic utility (B-73MI31 too). Substituted furan-2-carbaldehydes and 2-acylfurans on heating with ammonia and ammonium salts, often under pressure, yield 3-hydroxypyridines. The mechanism of this reaction is thought to involve nucleophilic attack of ammonia at the 2-position. Ring opening affords an amino aldehyde or ketone and thence, by reclosure, the 3-hydroxy-pyridine (Scheme 29). A wide range of substitutents is tolerated. Primary amines with furan-2-carbaldehydes yield A-substituted pyrroles, the closure of the intermediate... 

Azine approach. Cyclocondensation between 3-amino-4-hydroxypyridines and carboxylic acids leads to oxazole fusion as in (233) (77CR(C)(284)73>. The 2-phenyl derivative (235) has been obtained via a pyridyne-type reaction 3-benzamido-5-bromopyridine reacts with lithium piperidide via an intermediate which can be visualized as the pyridyne enolate (234) (73CB220). 

Azine approach. Diazotization of 2-amino-3-hydroxypyridines might be expected to yield the bicyclic ring system (631) by bond formation between the oxygen and the diazonium group in the first formed diazonium salt fused 1,2,3-thiadiazoles and -triazoles are formed by this type of reaction. Compounds prepared by this method, however, are highly unstable and have spectroscopic properties consistent with the pyridodiazooxide structure (630) (74CS(6)222>. 

Azine approach. The diazotization reaction of 3-amino-4-hydroxypyridine gives an unstable compound with spectroscopic properties consistent with the pyridodiazooxide form (632) <74CS(6)222>. 

Certain aromatic amines may cause reduction of Fe(III) ions in the presence of Fer-roZine Iron reagent (125), according to equation 18, leading to the formation of a stable violet-colored complex with Fe(II) ions (126), the concentration of which is measured at 562 nm. At pH 5, the color develops in a few minutes at room temperature and the absorbance of 126 is proportional to the concentration of the analyte. Neither the oxidation products of the analyte nor the excess of Fe(III) or 125 affect the assay however, not all aromatic amines undergo this reaction. Thus, compounds such as 1,4-phenylenediamine, 2,4-diaminotoluene, 8-aminoquinoline and 2-amino-3-hydroxypyridine can be determined... 

When 2- or 4-aminopyridine is diazotized, a-pyridone or y-pyridone is formed. Apparently, the diazonium salt reacts immediately with water to form a hydroxypyri-dine (Section 16.10). The product of the reaction is a pyridone because the keto form of a hydroxypyridine is more stable than the enol form. (The mechanism for the conversion of a primary amino group into a diazonium group is shown in Section 16.12). 

The dimethylamino group in diethyl (2 R=Et) and dimethyl 1-dimethylamino-3-oxobut-l-ene-2,4-dicarboxylates (2 R=Me) can be exchanged very easily with nitrogen nucleophiles. With primary amines in methanol or ethanol under reflux for several hours, substitution of the dimethylamino group by an amine takes place followed by intramolecular nucleophilic attack of the amino group on the ester to afford 1-substituted 5-alkoxycarbonyl-4-hydroxypyridin-2(lH)-ones 56 in 16-93% yields (5cheme 21). In the reaction of 56 with methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate (57), first the intermediate 58 was formed, which cyclized into 6-substituted 3-benzoylamino-8-ethoxycarbonyl-2H,5H-pyrido[4,3-li]pyran-2,5-diones (59). However, with 3-dimethyla-mino-2-(methoxycarbonyl)propenoate (60) intermediate 61 is formed... 

Compared to the Diels-Alder reactions of 5-alkoxyoxazoles, relatively few examples exist for intermolecular cycloadditions of aminooxazoles and their derivatives. Since the initial studies of 5-aminooxazoles by Kondrat eva only four others have been reported. 2-Amino-4-methyloxazole 66a reacted with diethyl maleate at room temperature in ethanol to provide a 35% yield of 67 and 11% of 68 (Fig. 3.19). The acetamide derivative 66b reacted with maleic anhydride at 50°C in toluene to give only the decarboxylated 3-hydroxypyridine 69. 

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