2-Pyridone derivatives, synthesis

Pyridone derivatives, synthesis using ketene dithioacetals 89-YGK413. 

Marazano and co-workers have also applied the reactions of tryptamine with various Zincke salts, including 115 (Scheme 8.4.39), in the synthesis of pyridinium salts such as 116. This type of product is useful for further conversion to dihydropyridine or 2-pyridone derivatives. For example, in a different study, Zincke-derived chiral pyridinium salts could be oxidized site-selectively with potassium ferricyanide under basic conditions as a means of chiral 2-pyridone synthesis (117 —> 118, Scheme 8.4.40). 

Synthesis, pharmacology, and molecular modeling of 2-pyridone derivatives as inotropic agents 97F331. 

Two new pyridone derivatives (14) and (15) have been prepared by cycloaddition of saccharin pseudochloride (16 R = Cl) with Danishefsky s diene and by treatment of (16 R = Me) with ciimamoyl chloride. The synthesis of two more ting expanded derivatives (17) and (18) via cycloaddition to benzisothiazoles was also described <96T3339>. 

The synthesis of cis-1,4 polymers was also tried by e use of monomers with an s-cis conformation. The solid-state photopolymerization of pyridone derivatives, which is a six-membered cyclic diene amide and is a tautomer of 2-hydroxypyridine, was attempted [100]. Pyridones make hydrogen-bonded cocrystals with a carboxylic acid in the crystalline state. Because the cyclic structure fixes its s-cis conformation, if the polymerization proceeds, a cis-2,5 polymer would be obtained. Actually, however, the photopolymerization did not occur, contrary to our expectation, but [4-1-4] photodimerization proceeded when the carbon-to-carbon distance for the dimerization was small (less than 4 A) [101]. A closer stacking distance of the 2-pyridone moieties might be required for the topochemical polymerization of cychc diene monomers. 

Ciclopirox olamine (Loprox) is a pyridone derivative available for the treatment of cutaneous dermatophyte infections, cutaneous C. albicans infections, and tinea versicolor caused by Malassezia furfur. It interferes with fungal growth by inhibiting macromolecule synthesis. 

Scheme 8.32 Iron-mediated synthesis of 2-pyridone derivatives.

Fused pyranone derivatives are converted into the corresponding fused pyridone derivatives by the action of an appropriate amine. Thus, heterocycle (308) yields naphthyridone (417) in moderate yield when reacted with ethanolic ammonia solution <62JCS4528>. Compound (418) and tryptamine gives the indole derivative (419) (82% yield) <76H(4)247>, which was used in the synthesis of nauclefine (420), and compound (421) and tryptamine gave heterocycle (422) (80% yield) <75H(3)627>, which was used in the synthesis of angustine (423). 

Patent Pyridone Derivatives, Their Preparation and Their Use as Synthesis... 

A Dewar isomer of unsubstituted pyridine was identified by Wilzbach, but it was very unstable.63 Other Dewar isomers of six-membered heterocycles, isolated and fairly stable, are substituted with perfluoroalkyl groups. However, 1,2-dihydroheterocyclic compounds such as a-pyrone or a-pyridone derivatives are easily photoisomerized to bicyclic Dewar isomers, which are useful for the synthesis of cyclobutadienes. The photochemistry of 1,2-dihydroheterocyclic compounds will be discussed, followed by those of fully aromatic compounds. 

Photoreactions of Pyridones - The pyridone derivative (122) undergoes ready (2 + 2) head-to-head photochemical addition when irradiated in acetone. The reaction appears to be very facile and requires only 16 minutes irradiation at 5°C to give a 79% yield of the adduct (123) which has been used as the starting material in a total synthesis of (-)-perhydrohistrionico-toxin (124). 

Various approaches to the synthesis of 2,7-naphthyridines are available. Thus, the dianilide of 3-oxoglutaric acid 133 reacted with malononitrile in the presence of sodium acetate to give pyridone derivative 134, whereas the reaction of 133 with ethyl cyano-acetate in pyridine afforded tetrahydropyridinedione derivative 135. The compounds 134 and 135 underwent cyclization upon heating with triethylamine in DMF to form substituted 2,7-naphthyridine-3,6-diones 136 and 137, respectively (1989JPR745). 

Hoffman, J.M., Smith, A.M., Rooney, C.S., et al. (1993) Synthesis and evaluation of 2-pyridone derivatives as HIV-1-specific reverse transcriptase inhibitors. 4. 3-[(Benzoxazol-2-yl) ethyl]-5-ethyI-6-methylpyridin-2(lH)-one and analogues. J. Med. Chem. 36 953-966. 

Thermal treatment of 2-pyridone derivatives, such as (76), with dimethyldichlorosilane, triethylamine and chloranil in benzene gives 8-hydroxyquinoline (77) in high yield by oxidative intramolecular [4+2] cycloaddition (Scheme 40) <94CC701). These isoquinolines are used in the synthesis of fully functionalized DEF rings of fiederimycin A. 

Progress in the synthesis of4-hydroxy-2-pyridone derivatives 12CJ0651. Recent progress in the synthesis of pyridinylboronic acids and esters 13ABJC(1)135. 

G. M. Ziarani, S. Mousavi, N. Lashgari, A. Badiei, J. Chem. Sci. 2013, 125, 1359-1364. Mesostructured SBA-15-Pr-SOjH an efficient solid acid catalyst for one-pot and solvent-free synthesis of 3,4-dihydro-2-pyridone derivatives. 

The synthesis of 2-pyridone derivatives from amines and 3-( )-methyl 3-(4-oxo-4//-chromen-3-yl)acrylate has been described (Scheme 79). ... 

The l-fiT-pyrano[3,4-c]pyridine nucleus is found extensively amongst alkaloids and a short photochemical synthesis has been reported, starting from readily available 4-acetoxy- or 4-alkoxy-2-pyridones (54). Under photochemical stimulation, these compounds react with the diethyl acetal of acrolein. Treatment of the head-to-tail adducts (55) with a base gives the cyclobuta[c]pyridone derivative (56), which rearranges (upon heating in acid) to produce the H-pyrano[3,4-c]pyridone (57). The method is claimed to be general. 

A third synthesis which has resulted in the preparation of rieinine and a number of its derivatives is due to Schroeter, Seidler, Sulzbacher and Kanitz,i2 who foimd that cyanoacetyl chloride polymerises spontaneously to 6-chloro-2 4-dihydroxy-3-cyano-pyridine. The di-sodium derivative of this with methyl sulphate produces A -methyl-6-chloro-4-hydroxy-3-cyano-2-pyridone (6-chlororicininic acid), the mono-sodium derivative of which, with methyl bromide or sulphate, is converted into 6-chlororicinine and the latter is reduced by zinc and sulphuric acid to rieinine. A fourth synthesis, starting from 3-nitro-4-pyridone, is due to Reitmann. ... 

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