3- Aryl pyridines, formation

An alternate approach to the formation of pyridylboronic acids is the cross-coupling of a halopyridine with a diboronate ester (usually bis(pinacolato)diboron, 7.7.)9 The analogous reaction of 2-chloropyridine led to pyridine formation through protodeboronation. The product of the reaction, either after hydrolysis to the boronic acid or in the ester form, can be further reacted with another aryl halide to give a biaryl. In certain cases the reaction might also be carried out in a one-pot manner.10... 

Palladium-catalysed directed C-H oxidation with (diacetoxy)iodobenzene of a series of meta -substituted aryl pyridine and aryl amide derivatives resulted in the formation of the corresponding acetoxy compounds. The reactions generally proceed with high levels of regioselectivity for functionalization of the less sterically hindered ortho-C-H bond.144 The mechanism shown in Scheme 4 has been proposed for the oxidation of 2,6-dimethylphenol with (diacetoxyiodo)benzene for the formation of 3,5,3, 5 -tetramethyl-biphenyl-4,4 -diol, via C-C coupling.145... 

The t-butylimines of o-iodobenzaldehydes and 3-halo-2-alken-l-ones can be reacted with terminal alkynes in the presence of a Pd/Cu catalyst to afford isoquinolines and pyridines in a process which apparently involves aryl alkyne formation, followed by cyclization with fragmentation of the f-butyl group (Eq. 18) [51,52]. 

Coordination of palladium with the adjacent pyridine ring is likely to facilitate the acylation of 2-arylpyridines with ct-diketones. In the presence of t-butyl hydroperoxide (TBHP), cleavage of the diketones yields radicals that may allow the formation of intermediates such as (115), which yield the acylated products after reductive elimination. Interestingly the ortfto-aroylation of 2-aryl pyridines may also be achieved using the palladium-catalysed reaction with toluene in the presence of TBHP. Here the mechanism is likely to involve initial benzylation followed by oxidation at the benzylic position to give the acylated product. Acetanilides may also be acylated at the ort/jo-position using toluene and TBHP to yield products such as (116). Here a possible mechanism involves initial formation of a cyclopalladated intermediate followed by reaction with an acyl radical formed by oxidation of the toluene. ... 

A large number of Brpnsted and Lewis acid catalysts have been employed in the Fischer indole synthesis. Only a few have been found to be sufficiently useful for general use. It is worth noting that some Fischer indolizations are unsuccessful simply due to the sensitivity of the reaction intermediates or products under acidic conditions. In many such cases the thermal indolization process may be of use if the reaction intermediates or products are thermally stable (vide infra). If the products (intermediates) are labile to either thermal or acidic conditions, the use of pyridine chloride in pyridine or biphasic conditions are employed. The general mechanism for the acid catalyzed reaction is believed to be facilitated by the equilibrium between the aryl-hydrazone 13 (R = FF or Lewis acid) and the ene-hydrazine tautomer 14, presumably stabilizing the latter intermediate 14 by either protonation or complex formation (i.e. Lewis acid) at the more basic nitrogen atom (i.e. the 2-nitrogen atom in the arylhydrazone) is important. 

Heterocyclic bases which readily form quaternary salts with the more usual reagents will also react with suitably activated aryl and heterocyclyl halogen compounds, the classic case being the salt formed from pyridine and l-chloro-2,4-dinitrobenzene. Reactions of this type have been studied by Chapman et Salt formation between... 

Cyclization of the 5-(A -arylcarboxamido)-4-hydrazino-6methylpyrim-idin-2-ones 104 with two molar equivalents of formaldehyde in the presence of pyridine caused the concomittant triazole and pyrimidine ring formation to yield the 4-aryl-l,3,4,10-tetrahydro-6-methyl-l,2,4-tria-zolo-[2,3,4-c,d]pyrimido[4,5-d]pyrimidine-5,8-diones 105 (89AP599)... 

Heterocyclization by catalytic formation of N—Car bond to give indoles, amino-pyridines, and N-aryl-substituted saturated heterocycles 98ACR805. 

There is evidence from a detailed study of the photolyses of 2-alkyl-substituted aryl azides 40 in diethylamine that A3,7V-diethyl-1 //-azepin-2-amines are formed as oxygen-sensitive, meta-stablc intermediates that can give rise to a variety of byproducts, including 5-acyl- A%V-diethyl-pyridin-2-amines and 6-alkyl-7-(diethylamino)-2//-azepin-2-ones 11 however, formation of these oxidation products can be avoided by refluxing the photolysate mixture with methanol prior to exposure to oxygen, in which case practicable yields of the /V,/V-diethyl-3W-azepin-2-amines 41 result. 

Examples of the intermolecular C-P bond formation by means of radical phosphonation and phosphination have been achieved by reaction of aryl halides with trialkyl phosphites and chlorodiphenylphosphine, respectively, in the presence of (TMSlsSiH under standard radical conditions. The phosphonation reaction (Reaction 71) worked well either under UV irradiation at room temperature or in refluxing toluene. The radical phosphina-tion (Reaction 72) required pyridine in boiling benzene for 20 h. Phosphinated products were handled as phosphine sulfides. Scheme 15 shows the reaction mechanism for the phosphination procedure that involves in situ formation of tetraphenylbiphosphine. This approach has also been extended to the phosphination of alkyl halides and sequential radical cyclization/phosphination reaction. ... 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

Generally, N -acylsulfonamides are less effective than those having a single N -aryl group. One such acyl analogue, sulfabenzamide (130) is prepared simply from sulfanilamide (128) by bisbenzamide formation (to 129) using benzoyl chloride and pyridine,... 

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