Pyridines 1-alkoxy carbonyl

As mentioned above, amines of the thienopyridine series synthesized by the Thorpe reaction always contain an electron-withdrawing substituent (acyl, alkoxy-carbonyl, etc.) at position 2. The presence of the o-aminocarbonyl fragment in these compounds makes these compounds useful as synthons for pyridine ring construction in the Friedlaender synthesis. Generally, condensation occurs in the presence of a basic catalyst. The acid-promoted synthesis can be exemplified by the preparation of tetracyclic structure 59 from pyranothienopyridine 60 (1996RFP1417446). 

Many analogs of 75 with substituents in the pyridine rings have also been prepared ° although 6-alkoxy-2,2 -bipyridines react with ethylene dibromide to afford the pyridone 76 rather than 4-alkoxy analogs of 75. Derivatives of 75 with alkyl substituents on the ethylene bridge (i.e., 6 and/or 7 positions) can likewise be prepared from 2,2 -bipyridines and appropriate dibromoalkanes. " " 6-Hydroxy-substituted derivatives of 75, for example, compound 78, are accessible by ring closure of j8-carbonyl monoquaternary salts of 2,2 -bipyridine, such as compound 77, with acid. 

Quaternization of molecules containing alkoxy and thioalkoxy substituents can be complicated by dealkylation of the substituent. Such side reactions are especially facile in molecules that give rise to a carbonyl or thiocarbonyl group following dealkylation. The reaction between a 2-substituted pyridine and Mel is illustrative [Eq. (16)]. This sequence is reversible and can be used to advantage to compare the enthalpies of unquaternized starting material and product.137,138... 

In the first case [1] Y can be either a hydroxy, alkoxy or nitro group. The first two groups are important but variable constituents in coals and the last is probably minor or non-existent. The second active class of species are the alkyl-pyridines [2]. The final case [3] includes substituents on the benzyl carbon where X can be an ether or carbonyl functional group. The general mechanism of this reaction is most probably the base catalyzed iodination of the benzyl carbon with subsequent displacement of the iodide by the pyridine to form the pyridinium salt. In all three modes of activation, the single aromatic ring can be replaced with polycyclic rings. 

The great significance of the later discovery, that exactly comparable additions to iV-aUcoxycarbonyl- or iV-aryloxycarbonyl-pyridinium cations, generated and reacted in situ, is that the dihydro-pyridines that resnlt are stable, and can be further manipulated. If re-aromatisation " is required, the iV-substituent can be easily removed to give a substituted pyridine. It is worth noting the contrast to the use of A-acyl-pyridinium salts for reaction with alcohol, amine nncleophiles (8.1.1.7), when attack is at the carbonyl carbon the nse of an iV-alkoxy/aryloxycarbonyl-pyridininm salt in the present context diverts attack to a ring carbon. 

Pyridine and 2,6-lutidine are useful as acid scavengers in the chlorination of a, 8-unsaturated ketones and esters. For the ketones, the pyridine bases typically favor the Markovnikov isomer however, for esters, pyridine shows little effect on the Markovnikov (alkoxy adjacent to carbonyl)/anti-Markovnikov isomer ratios (eq 14). ... 

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