1 -Hydroxypyridine-2-thione, reaction

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. ... 

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]. 

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... 

Perhaloalkanes serve as bromination or iodination agents in the radical decarbox-ylative halogenation of carboxylic acids. In an interesting modification of the Hunsdiecker-Bodin reaction Barton and coworkers have applied iV-hydroxypyridine-2-thione esters as nonelectrophilic intermediates for the decarboxylative bromination and iodination of primary, secondary and tertiary aliphatic and alicyclic592, as well as aroma-... 

Decarboxylation of the aliphatic esters of A-hydroxypyridine-2-thione by tributyltin hydride leads to reduction of the radical and the formation of the alkane lacking the carboxyl carbon, as in the Barton-McCombie reaction (Scheme 3.61). 

A new decarboxylative route to free radicals, which has proved particularly successful in preparative work, embodies the thermal (or photochemical) decomposition reaction of 1-hy-droxypyridine-2(l/f)-thione esters 23 with tributyltin hydride, /er/-butanethiol, or a similar hydrogen donor.These esters can be easily prepared from acyl halides and the sodium salt of l-hydroxypyridine-2(l//)-thione, or from the carboxylic acid, dicyclohexylcarbodiimide and l-hydroxypyridine-2(l/f)-thione. The intermediate radicals were readily reduced to the corresponding hydrocarbons 24 in efficient chain reactions with organotin hydrides or thiols as reaction partners, and the proportion of rearranged to unrearranged products could be controlled by the choice of hydrogen donor, its concentration and the temperature. This system was sufficiently quantitative and well behaved for use in kinetic studies, and the rate constants of the (S-scission reactions of the listed cyclopropylmethyl species were determined. 

The last, but certainly not the least, is the Barton modification to the Hunsdiecker reaction.24-26 It involves decomposition of thiohydroxamate esters in halogen donor solvents such as CCU, BrCCh, CHI3, or CH2I2 promoted by a source of radical initiation, which could be radical initiator (e.g., 18—>20),24 thermal (e.g., 21—>22),25 or photolytic26 conditions. The Barton modification is highly compatible with most functional groups. For example, under photolytic conditions, acid 23 was converted to acid chloride 24, which, without isolation, was treated with the sodium salt of Z/-hydroxypyridine-2-thione (19) with bromotrichloromethane as solvent to give alkyl bromide 25 in 90% yield.26... 

The iV-hydroxypyridine-2(///)thione derivatives (PTOC carbamates and PTOC imidates) permit facile generation of neutral, protonated, Lewis acid-complexed aminyl radicals and amidyl radicals. For cyclization reactions, the PTOC protocol was comparable or superior in yield to those involving Af-chloro or Al-thioaryl compounds. The thioxothiazolyloxycarbonyl (TTOC) carbamates containing a primary amine group would appear to be the most useful precursors now available for generating monoalkylaminium cation radicals [55]. Some representative examples are collected in Table 6. 

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. 

An alternative procedure for reductive decarboxylation without the use of trialkyltin hydrides as hydrogen atom donors has been developed Alkane carboxylic acid esters derived from AT-hydroxypyridine-2-thione decomposed to alkyl radical, which can readily accept a hydrogen atom from t-BuSH (equation 74) to give alkanes. This reaction can be conveniently performed as a one-pot experiment wherein the acid chloride of an alkane carboxylic acid, the sodium salt of thiohydroxamic acid, t-BuSH and 4-dimethyl-aminopyridine (DMAP) in benzene solution are heated to reflux. This procedure works well for COOH groups attached to primary and secondary carbon atoms. Instead of AT-hydroxypyridine-2-thione, one can use other thiohydroxamic acids, viz. iV-hydroxy-AT-methylthiobenzamide, 3-hydroxy-4-methylthiazole-2(3if)-thione (equation 75) and l-iV-hydroxy-3-AT-methylbenzoylenethiourea for decarboxylation reactions. 

Preparative Methods generally, 2,2 -dipyridyl disulfide-A, A -dioxide is obtained by the oxidation of fV hydrox3fp3Tidine-2-thione (2-mercaptopyridine-1-oxide, thiohydroxamic acid). To a suspension of 42.3 g of )V hydroxypyridine-2-thione in water (300 mL) was added 30% hydrogen peroxide (35 mL). The reaction is slightly exothermic. The reaction mixture was stirred for 1 h with the tenqterature maintained at 45 °C. A white solid,... 

Preparation of Disulfides. Unsymmetrical alkyl and aryl P3nidyl disulfide-A oxides are prepared by the reaction of 2,2 -dipyridyl disulfide-A,)V-dioxide with various thiols in good yields (eq 2). 7V hydroxypyridine-2-thione is a by-product of this reaction. 

This method works also for electron-rich aromatic and a,/8-unsaturated carboxylic acids and requires neither heavy metals nor strong oxidants. Among the various thiohy-droxamic esters investigated, A-hydroxypyridine-2-thione derivatives are exceptionally efficient. They are conveniently available by reaction of the respective acyl chloride with the sodium salt of A-hydroxypyridine-2-thione or by DCC-mediated coupling of the free acid. The Barton reaction gives the best yields of bromo derivatives the corresponding iodo derivatives are produced in much lower yields. Chlorine donors do... 

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. 

Among the most popular chromophores that usually offer the mildest and highest yielding radical-forming reaction is the N-hydroxypyridine-2(lH)-thione 1 (Scheme 2). It is interesting to notice the... 

Similar to esters derived from N -hydroxypyridine-2(lH)-thione 1, the O-esters of 4-methyl and 4-phenyl N-hydroxythiazoline-2-thiones (7a and 7b) undergo smooth thermal decarboxylative rearrangement in refluxing toluene but require UV photolysis at -320 nm (medium mercury pressure) for the photochemical reaction. 

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. 

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,... 

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