2-Aminopyridine, hydrogenation

Bromine Catechol Ally I cyanide Sulfuric acid 4-Aminopyridine Hydrogen Furmaric acid... 

Fluoropyridine. This isomer can be prepared in 54—81% yield by dia2oti2ation of 4-aminopyridine in anhydrous hydrogen fluoride (370,371,400). Eree 4-fluoropyridine readily undergoes self-quaterni2ation to give pyridyl pyridinium salts (401) stabili2ation can be effected as the hydrochloride salt (371,400). Numerous 4-fluoropyridinium salts, eg, 4-fluoro-l-methylpyridinium iodide, have been converted to novel penicillins (387,402). 

The structure of malonyl-a-aminopyridine (cf. 121) has been discussed by Snyder and Robinson/ who interpreted the infrared and ultraviolet spectra and the fact that it could be converted into a monochloro derivative (122, R = Cl) to indicate that the intra-molecularly hydrogen-bonded hydroxy form 122 (R = OH) was predominant. However, comparison of the basicities of the methoxy compound 122 (R = OMe), the mesomeric betaine 123 (R = Me), and the parent compound indicates that in aqueous solution the last exists mainly in the zwitterion form 123 (R = H), ... 

Chloroethyl)-3-[ (2-methyl-4-aminopyridin-5-yl)methyl] urea Sodium nitrite Hydrogen chloride... 

The reaction is not limited to Z—CH2—Z compounds. Other acidic CH hydrogens, which include, for example, the methyl hydrogens of a-aminopyridines, the methyl hydrogens of ynamines of the form CH3CSCNR2 (the product in this... 

Some unusual transformations will follow. The term unusual refers to unexpectedly smooth processes of H atom replacements obtained with (TMS)3SiH under radical conditions. Reaction (4.42) reports the replacement of a pyridinium moiety by hydrogen, with (TMS)3SiH under standard experimental conditions using t-BuOH as the solvent. In fact the two substrates (R = Me, Et) afforded 3-fluoro-2-aminopyridine derivatives in good yields [78], leaving the fluorine substituent untouched. 

The hydride released appears to abstract a proton from the product since the other product of the reaction is gaseous hydrogen. The aminopyridine anion is finally quenched with water. The product is mainly 2-aminopyridine, probably the result of the enhanced inductive effect on carbons immediately adjacent to the electronegative nitrogen. 

A classic reaction of this type is Chichibabin amination. leading mainly to 2-aminopyridine (Scheme 2.12a). This takes place when a pyridine is heated at 140 °C with sodamide (NH2 is a very strong nucleophile). Although hydrogen gas is certainly evolved during the reaction, the initial proton donor is not known. However, once some 2-aminopyridine is formed this product could function as the donor (Scheme 2.12b), and the process may then become a form of chain reaction. 

Peracchia C Effects of the anesthetics heptanol, halothane and isoflurane on gap junction conductance in crayfish septate axons A calcium- and hydrogen-independent phenomenon potentiated by caffeine and theophylline, and inhibited by 4-aminopyridine. J Membr Biol 1991b 121 67-78. 

To see whether water could be activated and added to Jt-systems other than alkynes, the metal-catalyzed hydrolysis of nitriles was studied [20]. For this purpose novel homodimeric and heterodimeric bis(acetylacetonato)ruthenium(ii) complexes bearing the 6-diphenylphosphino-N-pivaloyl-2-aminopyridine (10a) and 3-diphenylphosphinoisoquinolone (Ila) ligands were prepared. The molecular structures of these precatalyst were studied in solution and also in the solid state and revealed some unusual hydrogen-bonding patterns, in particular for the heterodimeric system in which the acetylacetonato ligand is involved (Scheme 2.7). 

To extend the concept to combinatorial asymmetric catalysis a new library of chiral aminopyridine and isoquinolone systems equipped with phosphine and phospho-nite donors was prepared and applied to the asymmetric rhodium-catalyzed hydrogenation (Scheme 2.8) [21],... 

Twelve different chiral aminopyridine and isoquinolone ligands (Figure 2.7) were synthesized and screened against the asymmetric hydrogenation of the standard test... 

A group from Spain patented a similar synthesis of risperidone (1) using similar synthetic transformations but in a different sequence (Scheme 2). Reaction of 2-aminopyridine with 2-acetylbutyrolactone in polyphosphoric acid at 160 °C afforded alcohol 15, which was hydrogenated to 16 and then converted to chloride 10 with thionyl chloride. Benzoyl piperidine 19 was prepared in a similar manner as in Scheme 1. In contrast to Scheme 1, 19 was alkylated with 10 prior to conversion to the 1,2-... 

Aminopyridine can be prepared by the reaction of 4-chloro-l,3-benzoxazines (47) with pyridine TV-oxides. Here it is proposed that an ion or radical pair is formed initially, which through displacement of hydrogen chloride and rearrangement leads to an TV-substituted benzoxazine (48). Finally, acid hydrolysis gives 2-aminopyridine and salicylic acid (49 Scheme 14) (80CPB465). 

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