N-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. 

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). 

Newcomb and coworkers have very elegantly demonstrated that N-hydroxypyridine-2-thione carbamates lc (PTOC carbamates, X = NR2) are directly analogous to the A-hydroxy-pyridine-2-thione esters la. They can be prepared readily from primary and secondary amines. Reaction of these carbamates in a radical chain process gives carbamoyl radicals that decarboxylate to give aminyl radicals, Scheme 40.66 71 In the... 

Decarboxylation. Acid chlorides react with the sodium salt of 1 (DMAP catalysis) to form esters (2) derived from N-hydroxypyridine-2-thione. These esters undergo radical chain decarboxylation to the noralkane on heating with tri-n-butyltin hydride (equation I). ... 

The N-hydroxypyridine-2-thione esters of Boc-protected amino acids undergo decarboxylation on photolysis in the presence of a hydrogen-atom-transfer reagent such as t-butyl mercaptan in 80-95% yield. Decarboxylation of the side-chain carboxy groups of suitably protected aspartic and glutamic acids can also be effected, but yields are lower (50-80%). ... 

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

In addition to dehydroxylation, a useful protocol for decarboxylation has been developed. The procedure was introduced by Barton, using thiohydroxamic esters 9, prepared from activated carboxylic acids (RCOX) and the sodium salt of N-hydroxypyridine-2-thione. Simple thermolysis or photolysis of the esters (homolysis of the N—O bond) results in the production of alkyl radicals R, which can attack the sulfur atom of the thiocarbonyl group to propagate the fragmentation (4.9). 

Another useful chain reaction involves the PTOC (pyridine-2-thione-N-oxycarbonyl) esters developed by Barton. Reaction of a carboxylic acid chloride (RCOCl) with the sodium salt on N-hydroxypyridine-2-thione produces an ester designated as R-PTOC. Addition of radical Y" (formed by an earUer initiation step) to the R-PTOC leads to the carboxy radical RCOj. The carboxy radical then decarboxylates to produce the radical R, which can continue the chain reaction or can undergo other reactions. 

Decarboxylation. - Barton s group has further extended their studies of radical-based decarboxylations in a number of ways (Scheme 10). One-carbon degradations of acids, RCO2H, to alkanes, RH, can be simply achieved by conversion into the thiohydroxamic esters derived from N-hydroxypyridine-2-thione followed by heating in benzene or toluene in the presence of t-butyl thiol.This avoids the use of more expensive tin hydrides which produce organostannane by-products which can be difficult to remove. By changing the traps available to the... 

The acyl derivatives of AT-hyroxypyridine-2-thione are a synthetically versatile source of free radicals. These compounds are readily prepared from reactive acylating agents, such as acid chlorides, and a salt of the N-hydroxypyridine-2-thione. 

The esters of N-hydroxypyridine-2-thione have proven to be a versatile source of radicals. The radical is formed by fragmentation of an adduct resulting from attack at sulfur by the chain-carrying radical. The generalized chain sequence is as follows ... 

Interestingly, alkyl radicals can be generated along the polymer backbone in the presence of monomer and nitroxide via a bimolecular process. The preparation of polypropylene (PP) functionalized by hydroperoxide by means of y-irradiation was reported. The resulting macroperoxide was then heated up to 125 °C in the presence of styrene or a styrene/butyl methacrylate mixture to produce the desired PP-g-PS or PP-g-P(S-co-BMA), respectively. Daly et a . and Daly and Evenson used esters of N-hydroxypyridine-2-thione or Barton esters to produce radicals on a polymer backbone under UV irradiation. This was successfully applied to poly (arylene ether sulfone) or hydroxypropyl cellulose backbones. ... 

AveUne, B. M., Kochevar, 1. E., and Redmond, R. W., Photochemistry of N-hydroxypyridine-2-thione derivatives involvement of the 2-pyridylthiyl radical in the radical chain reaction mechanism,/. Am. Chem. Soc., 117, 9699-9708, 1995. 

The thione function of the Barton ester 1 can be replaced by other elements such as Se (13) without significant alteration of the reactivity (Scheme 6). Although the starting esters are more air sensitive than the analogous N-hydroxypyridine 2-thione derivatives (1), the method has some advantages for example, the adducts of the free-radical fragmentation reactions of N-hydroxypyridine-2-selenone derivatives 13 (i.e., alkylpyridylselenides) can usually be more easily modeled and transformed to other chemical functions than thioethers. 

Reszka, K. J. and Chignell, C. F., Photochemistry of 2-mercaptopyridines. 3. EPR study of photoproduction of hydroxyl radicals by N-hydroxypyridine-2-thione using 5,5-dimethyl-l-pyrroline N-oxide in aqueous-solutions Photochem. Photobiol, 61, 269, 1995. 

Barton, D. H. R. and Samadi, M., The invention of radical reactions. 25. A convenient method for the synthesis of the acyl derivatives of N-hydroxypyridine-2-thione, Tetrahedron, 48, 7083,1992. Garner, R, Anderson, J. T. and Dey, S., S-(l-oxido-2-pytidinyl)-l,l,3,3-tetramethylthiouronium hexafluorophosphate a new reagent for preparing hindered barton esters,/. Org. Chem., 63,5732,1998. Prabhakar, S., Lobo, A. M., and Santos, A., A, Convenient method for the synthesis of N-hydroxy thiobenzamides (C-arylthiohydroxamic acids). Synthesis, 829,1984. 

Newcomb, M. and Kumar, M. U., N-hydroxypyridine-2-thione carbamates. VII. Intermolecular addition and addition-cyclization reactions of aminium cation radicals. Tetrahedron Lett., 31,1675,... 

---