1- Hydroxypyridine-2- -thione

Silver(I) complexes with mixed donor S, 0-ligands have been described with 1-hydroxypyridine-2-thione (261),1437,1438 cyclo-L-methionylglycine,1439 acyclic polyethers (262),1440-1442 dithio- and trithio-oxalate,1443 or chlorosulfate.1444... 

Azoisobutyronitrile Cyclopropylmethyl 3-exo Cyclisation A-endo Cyclisation Collidine DEPO Diethylphosphine oxide DPT Density functional theory DTBP Di-tert-butyl peroxide EPHP AT-Ethylpiperidine hypophosphite PCI Functional group interconversions EiMPA Hexamethylphosphoramide EDA Lithium diisopropylamide MAP 4-Methoxyacetophenone PTOC AT-Hydroxypyridine thione TMM Trimethylenemethane trityl Triphenylmethyl... 

Recently, it has been demonstrated by Sweeney and co-workers that fi-lactones can also be prepared by radical 4-exo cychsation methodology [93], The intermediate 0-(alkenoyl)oxyalkyl radicals 101 could be prepared by tin hydride treatment of the corresponding (l-bromopropyl)cinnamate. However, best results were obtained with N-hydroxypyridine thione (PTOC) esters 100. In this case a toluene solution of the PTOC ester and BusSnH was slowly added by syringe pump to a heated flask irradiated with a timgsten lamp (Scheme 22). For precursors containing only one substituent at the terminus of the double bond the direct reduction was the main process. For precursors 100 with two phenyl or two arylthio substituents, 4-exo cyclisation of the intermediate C-centred radicals 101 was efficient and good yields of -lactones 103 were isolated, accompanied in each case by minor amounts of the direct reduction product. The bis-arylthio functionahty was particularly appropriate for further FGI. 

The acyl derivatives of A-hydroxypyridine-2-thione are a synthetically versatile source of free radicals. These eompounds are readily prepared from reactive acylating agents, sueh as acyl chlorides, and a salt of A-hydroxypyridine-2-thione ... 

Reductive decarbonylation and decarboxylation can be carried out by (TMSlsSiH using acyl chlorides, phenylseleno esters, or N-hydroxypyridine-2-thione esters. Examples are shown in Reactions (17)-(19). Hydrolysis of the methyl ester followed by decarbonylation at the C2 position of hexahydropyrro-loindole (+)-17 afforded the desired tricycle (+)-18 in 84% yield and >99% ee. ... 

The acyl selenide 19 affords the decarbonylated )S-lactam in good yield. A N-hydroxypyridine-2-thione ester 20 is used in the key step to construct the chiral cis-cyclopropane structure in compounds designed as antidopaminergic agents. The observed high cis selectivity is due to the hydrogen abstraction from the sterically demanding (TMSlsSiH, which occurs from the less-hindered side of the intermediate cyclopropyl radical. 

Aminyl radicals are produced by the sequence outlined in equation 114. The action of phosgene on the sodium salt of A-hydroxypyridine-2-thione yields the salt 326, which reacts with amines to give 327. The latter decompose to the radicals 328 on heating or irradiation380. 

Similar studies have recently been extended to aminopyridones and thiones and to aminopyrimidones (Barlin jmd Pfleiderer, 1971 Barlin, 1972). Protonation of 3- and 5-amino-2-hydroxypyridine and 3,4-diamino-2-hydroxypyridine occurs first at the 3- (or 5-) amino-group, but 4- and 6-amino-2-hydroxypyridine and 2- and 3-amino-4-hydroxypyridine first protonate at the oxygen atom, because the amino-group is involved in conjugation with the partially positively charged ring nitrogen. Similar results are found for the amino-pyridine-2(and 4)-thiones (Barlin, 1972). 

The esters of A-hydroxypyridine-2-thione are another versatile source of radicals.195 The radical is formed by decarboxylation of an adduct formed by attack at sulfur by the... 

A very efficient methodology for generating carbon radicals utilizes esters of A-hydroxypyridine-2-thione as radical precursors, and these have been used by Blood-... 

SCHEME 10. Preparation of hydroperoxides via oxygenation of carbon radicals generated from iV-hydroxypyridine-2-thione esters as radical precursors... 

The PE spectra of hydroxy- and mercapto-pyridines have been examined, together with the model iV-alkyl and S- or O-alkyl compounds, to elucidate the tautomeric equilibria in the vapor phase (77JCS(P2)1652) (Section 2.04.4.2). Figure 21 and Table 13 show details of the PE spectra of l-methylpyridin-2-one, 2-methoxypyridine and the tautomeric mixture at equilibrium of pyridin-2-one and 2-hydroxypyridine. This indicates that there is approximately 25% of oxo form present once adjustment has been made for the expected influence of methylation, similar measurements reveal ca. 10% of the thione form in the mercapto-thione equilibrium. Other spectra indicate that 3- and 4-hydroxy- and 3- and 4-mercapto-pyridine exist in the vapor phase with less than 5% of the alternative tautomer present. 

In line with Beak s finding, pyridin-2-one was estimated to be 31 kJ mol-1 less aromatic than the pyridine, and a similar figure of 25 was estimated for pyridine-2-thione. Subsequent results (73JCS(P2)1080, 76AHC(S1)71) on the pyridin-4-one, quinolin-2-one and isoquinolin-1-one series showed that aromatic resonance energy difference for the pyridin-4-one/4-hydroxypyridine system was very similar to that for the 2-substituted compounds, in contrast to Beak s findings. 

Reactions of 3-hydroxy-6-methyl-2(lfl)-pyridinethione with 1,3-dibromo-propanes in methanol in the presence of sodium methylate yielded betaines (205) (70ACS2949). 9-Hydroxy-3,4-dihydro-2f/-pyrido[2,l-6][1,3]-thiazinium bromide was obtained in the reaction of 3-hydroxypyridine-2(lH)-thione and l-bromo-3-chloropropane in boiling toluene [81JCR(S)208]. 

Another useful aspect of the radical chemistry associated with thiocarbonyl compounds is the decarboxylation of acids. Typically the acyl derivatives (2) of /V-hydroxypyridine-2-thione (1) are prepared from the appropriate acid [243], and treated with tributyltin hydride. 

It is also known that once the tributyltin radical adds to the sulfur of N-hydroxypyridine-2-thione, breakage of the N-0 bond and decarboxylation are very fast and probably concerted. They are driven energetically by formation of the very stable carbon dioxide molecule. It comes as no surprise that if atoms other titan carbon are attached to the carboxyl group, then they would also end up as free radicals after decarboxylation. This is shown for a urethane analog as a source of nitrogen-centered free radicals. A wide variety of other free-radical species can be produced by this strategy, and it is thus quite useful. 

Thus, considerable care has to be taken not to misinterpret photobiological studies using this OH-source. A further caveat has been expressed by Douki et al. (1999) who observed that product ratios are considerably different when ionizing radiation and N-hydroxypyridine-2-thione were used as -OH sources, and this has been explained by the H-donating property of the N-hydroxypyridine-2-thione (note the major dimers mentioned above). 

E. Aminyl Radicals from A -Hydroxypyridine-2(l//)thione Carbamates. 11... 

E. Aminyl Radicals from N-Hydroxypyridine-2(1H)thione Carbamates... 

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