Thiopyridones, and

Katritzky and Taft were the first to use ICR proton affinities for tautomeric studies (76JA6048). This and work of Katritzky and Nibbering (77TL1777) discuss the tautomerism of pyridones and thiopyridones and conclude that ICR results are in agreement with previous studies of Beak (76JA171)—that in the gas phase the OH and SH tautomers predominate. The complicated case of 2-thiouracil (six aromatic tautomers) was studied by Katritzky and Eyler [89JCS(P2)1499] they conclude that the oxothioxo tautomer is the most stable. 

Alkylation of 2-thiopyridone and of 2-thiobenzoxazolone has been described by Dou et al.195 Yields are good, and only S-alkylation is detected. In a later study, A4-thiazoline-2-thione, thiazolidine-2-thione (130) and benzothiazoline-2-thione have been alkylated, using the phase transfer technique.196... 

A mixture of O-acyl ester (1 mmol) of A-hydroxy-2-thiopyridone and benzoquinone (5-7 mmol) in degassed dichloromethane (20 ml) was irradiated with a 300 W tungsten lamp for 30 min. under a nitrogen atmosphere at 0 °C. After the reaction, the solvent was removed and the residue was chromatographed on silica gel to give 1,2-disubstituted benzoquinone [63]. 

Diisopropyl tellurium intercepted primary carbon radicals, generated by the photolysis of acyl derivatives of iV-hydroxy-2-thiopyridone, and released isopropyl radicals that were trapped by olefins2. 

Further, thiopyridones and quinaldinethiones can be obtained by the action of alkali hydrogen sulfides on halopyridinium and haloquinaldinium salts 325 326... 

Esters derived from iV-hydroxy-2-thiopyridone and, for example. -amino acids, react with vinylpho.sphonic diesters on irradiation to give complex pho.sphonic derivatives from which the thiopyridine group can be removed with tributylstannane. In... 

Protection of amino group. The o-nitrophenylsulfenyl group has been used for protection of side-chain amino groups in peptide synthesis. The classical method for removal is treatment with acid, even acetic acid, but this method is not selective. The selective removal is now possible by cleavage with 2-mercapto-pyridine (2-thiopyridone) and 1 equiv. of HOAc in CH3OH, DMF, or CH2Cl2. ... 

Unsymmetrical Disulfides. Unsymmetrical aryl and alkyl disulfides are prepared from silyl sulfides and MeSS02Me in CHCI3 at 60 °CP Methyl 2- and 4-pyridyl disulfide are prepared conveniently from 2- and 4-thiopyridone and MeSS02Me in the presence of NaOH in H2O in excellent yields. ... 

Steady-state kinetics. The reaction of methylthiamine (MT+) in the presence of a large excess of SO3 and of 4-thiopyridone (= ArS-) is believed to follow the mechanism shown here,15 in which A" and B are steady-state intermediates. Derive the steady-state rate law. 

In another version of this method, the radical generated by radical exchange from the aryl telluride carbohydrate 83 and the N-acetoxy-2-thiopyridone affords, after intramolecular cyclization and desulfanylation, the polyhydroxylated and phosphorylated pseudo sugar 84 [54] (Scheme 23). 

Fundamentally, O-esters of N-hydroxy-2-thiopyridone are photo-lyzed in the presence of an excess of white phosphorus in a methylene chloride/carbon disulfide medium. On solvent removal, hydrolysis, and oxidation with hydrogen peroxide, good yields of phosphonic acids (Figure 2.10) bearing the carbon functionality of the parent acid are isolated. 

Scheme 5-5. Reagents and conditions a NaOCE Ph, THF/DMF 5 1, — 10°C to room temperature, b LiAlELt, Et20, reflux, c AC2O, Py. d (1) Cat. RuCh/NaKTt, CCI4/ MeCN/H20 1 1 1.5, room temperature. (2) LiOH, THF/H20 5 4, 0°C. (3) 2N HC1, Et20, 0°C to room temperature, e (1) IV-methylmorpholine, isobutylchloroformate, N-hydroxy-2-thiopyridone, THF, NEt3, TFIF, — 15°C, (2) t-butyl mercaptan, irradiation, THF, room temperature, f H2, 10% Pd/C, EtOFI. g Cat. ( -Pr)4NRu04, NMO, 4 A MS, CH2CI2, room temperature.

Unfortunately, these dialkylaminopyridinium salts have limited utility in the presence of aqueous NaOH or Na S, even at moderate temperatures. Displacement of dialkylamlne and formation of 2-alkylpyridone or thiopyridone occurs within hours at 100 (Equation 3). 

It was discovered that the acetyl derivalive of iV-hydroxy-2-thiopyridone is especially suitable as a source of methyl radicals, being photolysed by irradiation with a simple tungsten lamp. On this basis, and because of the high radicophilicity of tellurides (especially anisyl tellurides), a radical exchange occurs when the reagent is irradiated in the presence of an... 

Protected L-Asp reacted with cyclohexyl bromide and was converted into an A-hydroxy-2-thiopyridone derivative. Photolysis at room temperature afforded a mixture of cyclic stereoisomers (Scheme 45), the stereochemistry of which was determined by NMR and X-ray analysis (87TL1413). 

A similar procedure has successfiiUy generated aminyl radicals by treating the iV-carbamates of Ar-hydroxyl-2-thiopyridones (40) with radical initiators such as RS- and RsSi-. The aminyl radical generated abstracts a proton or adds intramolecularly to the double bond to result in the cycli-zation products shown in Scheme 26 (87JA3163). 

From the practical point of view, alkylation of heteroaromatics with Barton decarboxylation of A-acyloxy-2-thiopyridones (17), prepared from carboxylic acids and Af-hydroxy-2-thiopyridone, is very useful, since it can be used for various kinds of carboxylic acids such as sugars and nucleosides [23-26]. This reaction comprises of the initial homolytic cleavage of the N-0 bond in A-acyloxy-2-thiopyridone to form an acyloxyl radical and PyS , (3-cleavage of the acyloxyl radical to generate an alkyl radical and C02, addition to the electron-deficient position of heteroaromatics by the alkyl radical to form the adduct, and finally, abstraction of a hydrogen atom from the adduct by PyS , as shown in eq. 5.10. 

A solution of A-adamantanecarbonyloxy-2-thiopyridone (145 mg, 0.5 mmol), cam-phorsulfonate salt of lepidine (1.23 g, 3.27 mmol), and dichloromethane (6 ml) was irradiated with a tungsten lamp (200 W, W-hv) under nitrogen atmosphere at the range of 20 25 °C for 1 h. After the reaction, the reaction mixture was poured into... 

To a solution of Af-hydroxy-2-thiopyridone (140 mg, 1.1 mmol) and pyridine (0.1 ml) in toluene (10 ml) was added a solution of 3(3-acetoxy-ll-ketobisnorallocholanic acid... 

The same reaction can be carried out by the dropwise addition of 3p-acetoxy-ll-ketobisnorallocholanic acid chloride (1 mmol) in toluene (5 ml) to a refluxing solution of dried sodium salt of V-hydroxy-2-thiopyridone (1.2 mmol), 4-(dimethylamino)pyridine (0.1 mmol), and tert-BuSH (4.5 mmol) in toluene (20 ml), over 15 min [1]. 

A solution of sulfur (S8, 74 mg, 0.29 mmol) and adamantanecarboxylate ester of N-hydroxy-2-thiopyridone (290 mg, 1 mmol) in dichloromethane (15 ml) was irradiated with a tungsten lamp for 1 h under a nitrogen atmosphere at 0 °C. After the reaction, a solution of NaBH4 (20 mmol) in methanol (10 ml) was added drop wise over 15 min to the reaction mixture at room temperature, and the mixture was stirred for one hour. After the reaction, 1 M sulfuric acid (60 ml) was added to the mixture, and then the solution was extracted with dichloromethane (4 X 20 ml), and dried over Na2S04. After removal of the solvent, the residue was purified by column chromatography on silica gel (eluent hexane/ethyl acetate = 97/3) to provide adamantanethiol in 88% yield [33]. 

To a solution of P,p-diphenylpropionic acid (2 mmol) in CHC13 (8 ml) were added oxalyl chloride (1.5 g) and DMF (one drop). After stirring for 1 h, the solvent and excess oxalyl chloride were removed. The residue was dissolved in CHC13 (6 ml) and then Af-hydroxy-2-thiopyridone (2.2 mmol) was added to the mixture under a nitrogen atmosphere at 0 °C. 

Unlike Af-hydroxy-2-thiopyridone, TV-hydroxy-2-selenopyridone is rather unstable and is easily oxidized. However, once photolytic treatment of O-acyl ester (53) of AMiydroxy-2-selenopyridone is carried out, the formed 2-pyridyl selenide is very useful. Thus, elimination of the selenoxides, formed from the oxidation of the selenide with mCPBA or ozone, proceeds effectively at low temperature. For example, eq. 8.23 shows the preparation of (l)-vinylglycine (56) from (L)-glutamic acid without racemization at all [70]. 

Carbonate and carbamate derivatives, prepared from the reaction of alcohols and amines with phosgene and /V-hydroxy-2-thiopyridone, provide the corresponding alkoxyl radicals and aminyl radicals respectively, via radical decarboxylation [71-81]. For example, photolytic treatment of carbamate (57) derived from 4-pentenylamine generates the corresponding 4-pentenylaminyl radical, as shown in eq. 8.24. Under neutral conditions in the presence of tert-BuSH, a direct reduction product (A) of 4-pentenylaminyl radical is formed, while, in acidic conditions, cyclized product (C), pyrrolidine, via 5-exo-trig manner from 4-pentenylaminyl radical is formed. Under the latter conditions, the real reactive species is an electrophilic 4-pentenylaminium radical which rapidly cyclized via 5-exo-trig manner. 

---