Pyridines 4-amino- from

Scheme 35 Formation of 2,5-disubstituted pyridines 162 from a,/ -unsaturated complexes with a primary 3-amino group 160 and alkynes 90 [36,88]...

B. 4-Phenyl-5-anilino-l,2,3-triazole. Six grams (0.025 mole) of 1,4-diphenyl-5-amino-l,2,3-triazole is dissolved in 20 g. of dry pyridine (distilled from solid sodium hydroxide) and heated under reflux for 24 hours (Note 6). The reaction mixture (Note 7) is poured into 11. of ice water. The product separates as a slightly yellowish milky oil which is converted to white needle-like crystals by stirring the mixture and scratching the beaker with a glass rod. The product is collected by suction filtration, washed with water, suction-dried, and recrystallized from aqueous ethanol (Note 8). The yield is 5.5-5.6 g. (92-93%) of fine white needle-like crystals, m.p. 167-169° (Note 9), soluble in hot water and ether, but difficultly soluble in benzene. 

Polarographic methods have been extremely useful for the determination of the urinary excretion of the 1,4-benzodiazepines. An assay that employs selective solvent extraction and acid hydrolysis of diazepam and its major metabolites, iV-desmethyldiazepam and oxazepam, to their respective benzophe-nones has been employed to measure the urinary excretion of diazepam [183]. A pulse polarographic assay has been reported that will measure the urinary excretion of bromazepam following a single 12-mg dose [184]. The assay employs selective extraction of bromazepam and the 2-amino-5-bromobenzoyl-pyridine metabolite from the deconjugated metabolites, 3-hydroxybromazepam and 2-amino-3-hydroxy-5-bromobenzoylpyridine, into separate diethyl ether fractions. The residues of the respective extracts are dissolved in phosphate buffer (pH 5.4) and analyzed by pulse polarography, which yields two distinct... 

Dihydropyridines are inherently unstable and rapidly isomerize to other dihydropyridine isomers many also rapidly eliminate H2 to form pyridines. The exceptions are 3,4-dihydropyridines substituted at the 2- and 5-positions with electron-donating groups. However, even stable 3,4-dihydropyridines can be oxidized to the corresponding pyridine by the use of 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) <1995T7161>. An example of the stability of these substituted 3,4-dihydropyridines is in the unexpected formation of 2-methoxy-3,4-dihydropyridine 45 rather than the expected pyridine 46 from the [3+3] cyclization of 4-amino-l-azabutadiene 44 with Fischer alkynylcarbene complex 43 (Equation 1) <2001NJC8>. The 2-methoxy group was proposed to stabilize an intermediate and result in elimination of the metal without aromatization. 

The preparation of pyridine compounds from a,o>-dinitrile systems has been studied by several workers. Johnson et al.101 found that 3-hydroxyglutaronitriles (128) or glutacononitriles (129) react readily with anhydrous hydrogen bromide or iodide to yield the 2-amino-6-halopyridines (130) as their salts, although in no case does hydrogen chloride cause cyclization to the expected 2-amino-6-chloropyridine. 

Azine approach. It is claimed that a stepwise procedure is required for the preparation of oxazolo[5,4-6]pyridines (246) from 3-amino-2(l//)-pyridinones firstly the amino group... 

Aiylpyridines. The amino group of aromatic amines can be replaced by the pyridyl group by the normal diazohydroxide reaction, by treatment of the sodium diazotate in pyridine with acetyl chloride, by adding the dry diazonium salt to pyridine, and from the nitrosoacetyl... 

If, on the other hand, an amino group can be introduced ortho to the nitro group, reduction of 202 or 203 makes available the starting materials for fused heterocycles. One example is the synthesis of imidazo[4,5-c]pyridines 205 from diamino pyridines such as 204. 

Saleh et al. [102] developed novel, simple, and efficient methods for the synthesis of pyrimido[l,2-fl]benzimid-azoles and pyrazolo[3,4-b]pyridines (131) from amino azoles (128), aldehyde (129), and p-ketosulfone (130) under ultrasonic irradiation (Scheme 33). The reaction was proposed to proceed via utilization of p-ketosulfone as a main synthon. The ultrasound reaction in ethanol was inefficient at catalyst-free condition and produced only 29% of the product after 90 min. Yields were 87-92% in 10-15 min and 81-97% in 30-60min for pyrimido[l,2-a]benzimidazoles and pyrazolo[3,4-b]pyridines, respectively, xmder the optimized conditions. 

Full details have been published of the synthesis of pyridines derived from the 1,5-dicarbonyl compounds resulting from the reaction of -ketoketene dithioacetals with the carbanions obtained by deprotonation of methyl ketones. 5 There have been two reports of the synthesis of pyridines from enamines and malononitrile.26,27 This route is exemplified by the conversion of the readily available enamines (10 Z=0 or S) into the 2-amino-3-cyanopyridines (11) ... 

The presence of certain substituents e.g., the amino group) may markedly affect the solubibty and other properties of the sulphonic acid or carboxylic acid. Thus such sulphonic acids as the aminobenzenesul-phonic acids, pyridine- and quinoline-sulphonic acids exist in the form of inner salts or zwitter-ions that result from the interaction of the basic amino group and the acidic sulphonic acid. Sulphanilic acid, for example, is more accurately represented by formula (I) than by formula (II) ... 

Chapter V. Quinaldine (V,2) 2-methyl-, 2 5-dimethyl- and 2-acetyl-thiophene (V,8-V,10) 2 5-dimethyl and 2 4-dimethyl-dicarbethoxy-p3nrole (V,12-V,13) 2-amino- and 2 4 dimethyl-thiazole (V,15-V,16) 3 5-dimethyl-pyrazole (V,17) 4-ethylp3rridine (from pyridine) (V,19) n-amyl-pyridines from picolines) (V,28) picolinic, nicotinic and isonicotinic acid (V,21-V,22) (ethyl nicotinate and p-cyanop3n idine (V,23-V,24) uramil (V,25) 4-methyl-(coumarin (V,28) 2-hyi-oxylepidine (V,29). 

Benzoyl chloride and derivatives acylate 2-amino-4-aryithiazoles in dioxane in yields of 80 to 90% (249, 250). The location of the acyl group on the exocyclic N has been demonstrated by the fact that the benzoyla-tion product is identical to the benzamidothiazole synthesized from benzamide and 2-bromothiazole (251). 3-Indolyl acetic acid chloride (89) acylates 2-aminothiazole in pyridine (Scheme 62) (81). 

---