Pyridines, acylation halogenation

Purine, 9- -D-ribofuranosyl-6-selenoxo- 1,6-dihydro-synthesis, 5, 597 Purine, 6-thiocyanato-acylation, 5, 559 Purine, 2-thioxo-synthesis, 5, 589 Purine, 8-thioxo-iodination, 5, 559 synthesis, 5, 577, 597 Purine, 2-thioxo-2,3-dihydro-synthesis, 5, 572 Purine, 6-thioxo-1,6-dihydro-acylation, 5, 559 dethiation, 5, 558 halogenation, 5, 559 hydrolysis, 5, 560 methylation, 5, 535 oxidation, 5, 560 synthesis, 5, 572, 596 Purine, 8-thioxo-7,8-dihydro-acylation, 5, 559 Purine, 2,6,8-trichloro-alkylation, 5, 530 amination, 5, 562 reactions, 5, 561, 562 with hydriodic acid, 5, 563 with pyridine, 5, 562 synthesis, 5, 598 Purine, 2,6,8-trichloro-7-methyl-synthesis, 5, 557 Purine, 8-trifluoromethyl-synthesis, 5, 574... 

Halogenation of the acetyl compound 14 affords the corresponding chloroketone (15). (Compound 14 is obtainable by acylation of the quinolol. The pyridine ring is, of course, deactivated in the acidic conditions of the reaction.) Displacement of halogen by means of isopropylamine leads to the aminoketone... 

Free radical acylation of pyridines generally results in predominant or exclusive formation of the 2- and 4-substituted isomers, and carbamoylation, carboxylation and halogenation show similar product distributions. In certain of these reactions, most notably carbamoylation, synthetically significant yields of substitution products can be realized, but in many cases while quoted yields can look impressive, actual conversions can be very low <74AHC(16)123>. 

A recent halogen-free benzofuran that shares many structural features with its predecessor shows activity in controlling arrythmias. The synthesis starts with an unusual scheme for building the furan ring. Reaction of the benzyl bromide (2-1) with triphenylphosphine leads to phosphonium salt (2-2). Treatment of the salt with valeryl chloride in the presence of pyridine results in acylation on the now highly activated benzylic carbon (2-3). That product cyclizes to the benzofuran (2-4) on heating with expulsion of triphenylphosphine. Friedel-Crafts acylation of (2-4) with anisoyl chloride in the presence of stannic chloride proceeds on the... 

The pyridine 122 reacts with BuLi by I/Li exchange capture of the lithium derivative with propanal and oxidation gives the ketone 130 in the heterocyclic equivalent of a Friedel-Crafts acylation. The fluorine atom that was originally present to initiate the halogen dance from 120 to 121 can now be hydrolysed to give the pyridone 126. 

These solid-acid catalysts are, in principle, applicable to a plethora of acid-catalyzed processes in organic synthesis [18]. These include various electrophilic aromatic substitutions, e.g. nitrations, halogenations, and Fiiedel-Crafts alkylations and acylations, and numerous rearrangement reactions such as the Beckmann and Fries rearrangements. Other examples include a variety of cyclization reactions such as Diels-Alder reactions and the synthesis of pyridines and other heterocycles. 

Friedel-Crafts Alkylation and Acylation. Just as for nitrobenzene, these reactions cannot be accomplished Halogenation. With two moles of aluminum chloride (one that complexes on nitrogen and the other to activate the halogen) and a reaction temperature of 80-115°C, pyridine can be chlorinated at the 3-position. These conditions also give some... 

Consequently, pyridine has a reduced susceptibility to electrophilic substitution compared to benzene, while being more susceptible to nucleophilic attack. One unique aspect of pyridine is the protonation, alkylation, and acylation of its nitrogen atom. The resultant salts are still aromatic, however, and they are much more polarized. Details for reactivity of pyridine derivatives, in particular, reactions on the pyridine nitrogen and the Zincke reaction, as well as C-metallated pyridines, halogen pyridines, and their uses in the transition metal-catalyzed C-C and C-N cross-coupling reactions in drug synthesis, will be discussed in Section 10.2. 

---