Pyridyl sulfides

Pyridyl)hydrazine (Aldrich), 4-acetylpyridine (Acros), N,N,N -trimethylethylenediamine (Aldrich), methylrhenium trioxide (Aldrich), InQj (Aldrich), Cu(N0j)2-3H20 (Merck), Ni(N03)2-6Il20 (Merck), Yb(OTf)3(Fluka), Sc(OTf)3 (Fluka), 2-(aminomethyl)pyridine (Acros), benzylideneacetone (Aldrich), and chalcone (Aldrich) were of the highest purity available. Borane dimethyl sulfide (2M solution in THE) was obtained from Aldrich. Methyl vinyl ketone was distilled prior to use. Cyclopentadiene was prepared from its dimer immediately before use. (R)-l-acetyl-5-isopropoxy-3-pyrrolin-2-one (4.15) has been kindly provided by Prof H. Hiemstra (University of Amsterdam). 

Treatment of pyridyl carbinol 51 with thionyl chloride leads to the corresponding chloride (52), Treatment of that intermediate with 5-methoxy-2-mercaptobenzimidazole (53), obtained from reaction of 4-methoxy-q-phenylenediamine with potassium ethylxanthate leads to displacement of halogen and formation of the sulfide (54). Finally, oxidation with 3-chloroperbenzoic acid produces the sulfoxide omeprazole (55) fl7]. 

Scheme 23. Barton s thiohydroxamate ester chemistry synthesis of alkyl pyridyl sulfides (127).

The rhodium-catalyzed hydroboration has opened the way to cyclization reactions starting from dienes [92], For instance, rhodium-catalyzed hydroboration of the terminal alkenyl group of an os/Tunsaturated lactone followed by reaction with the PTOC-OMe chain transfer reagent afforded the bicyclic a-S-pyridyl lactone in 63% yield (Scheme 39). After oxidation of the sulfide with m-CPBA, thermal elimination of the sulfoxide afforded the corresponding a-methylene lactone in 65% yield. Interestingly, such bicyclic a-methylenelactones are substructures that can be found in many natural products such as mirabolide [93]. 

Structural information on aromatic donor molecule binding was obtained initially by using H NMR relaxation measurements to give distances from the heme iron atom to protons of the bound molecule. For example, indole-3-propionic acid, a structural homologue of the plant hormone indole-3-acetic acid, was found to bind approximately 9-10 A from the heme iron atom and at a particular angle to the heme plane (234). The disadvantage of this method is that the orientation with respect to the polypeptide chain cannot be defined. Other donor molecules examined include 4-methylphenol (p-cresol) (235), 3-hydroxyphenol (resorcinol), 2-methoxy-4-methylphenol and benzhydroxamic acid (236), methyl 2-pyridyl sulfide and methylp-tolyl sulfide (237), and L-tyrosine and D-tyrosine (238). Distance constraints of between 8.4 and 12.0 A have been reported (235-238). Aromatic donor proton to heme iron distances of 6 A reported earlier for aminotriazole and 3-hydroxyphenol (resorcinol) are too short because of an inappropriate estimate of the molecular correlation time (239), a parameter required for the calculations. Distance information for a series of aromatic phenols and amines bound to Mn(III)-substituted HRP C has been published (240). 

Meyers and Ford (76JOCI735), and Hirai et al. (72CPB206) have used 2-(alkylthio)-2-oxazolines or thiazolines to prepare the corresponding thi-iranes upon treatment with bases and subsequently with carbonyl compounds. The reactions of 2-pyridyl sulfides are expected to proceed similarly as shown in Scheme 22, since the oxazoline ring is a good leaving group in the intramolecular substitution reaction. When optically active oxazolines are used, asymmetric induction takes place to afford the optically active thiiranes in 19-32% enantiomeric excess (ee). The process is shown in Scheme 23. 

Aliphatic and aromatic thiols react with pyridine 1-oxides and their quaternary derivatives by Type A, B and/or C pathways, but no such reactions have been reported for pyridine or its salts. 1-Ethoxypyridinium ethosulfate reacts with sodium n-propanethiolate to give mainly pyridine (Type A), and a 6 1 mixture of 3- and 4-pyridyl propyl sulfides (equation... 

Substituent R Method Yield (%) Pyridyl sulfides Isomer distribution 2- 3- 5- 6- Other products Yield (%)... 

An jco-OT o-cyclisation of a,o -diynes promoted by bis(pyridyl)iodonium(i) tetrafluoroborate (IPy2BF4) has been described for the first time and is an excellent route for accessing a variety of sulfur-containing heterocycles when employing alkynyl sulfides (Scheme 49) <1998AGE3136>. 

When favorable results in the case of allylic sulfones had been obtained, asymmetric synthesis of the cyclic sulfides 5a, 5ba, Sab and Sea (Scheme 2.1.4.9) and of the acyclic sulfides 6aa, Gab, 6ac, 6ba, and 6bb (Scheme 2.1.4.10) was investigated. As shown by Table 2.1.4.9, the pyrimidyl sulfide Saa could be obtained in medium to good yield (entry 1). Interestingly, the corresponding pyridyl sulfide Sab isolated from the reaction of rac-laa with 2-pyridinethiol had a much lower ee value (entry 2). The reaction of the cycloheptenyl carbonate rac-lba with 2-pyrimi-dinethiol afforded the sulfide Sba in a similar yield to the cyclohexenyl derivative... 

Furukawa et al.281 have compared the activity of pyridyl sulfones and sulfoxides with that of sulfides. 

Chloro-l-methylpyridinium iodide (683) functions as an important mediator in a variety of different reactions. Esters are formed in high yield from acids and alcohols when reacted with one equivalent of (683) in the presence of two equivalents of triethylamine (Scheme 158) (75CL1045). cv-Hydroxy acids are lactonized under similar conditions (76CL49). The pyridinium salt (683) will also convert thioureas into carbodiimides (77CL575) and pyridine-2-thiones to pyridyl sulfides (75CL1159). 

An efficient synthesis of thieno[2,3-c]pyridine starting from 4-vinylpyridine (275) has been described by Klemm and coworkers (Scheme 69) (68JHC883). Because 4-vinylpyridine and hydrogen sulfide under high-temperature conditions formed (259) only in very low yield, (275) was converted into benzyl pyridyl sulfide (276) prior to thermolysis. Thieno[2,3-c]pyridine is obtained as low-melting (m.p. 59-60 °C) yellow crystals. 

The basic transformation that underlies the Barton method is outlined in Scheme 45, steps 1 and 2.152 Thermolysis in refluxing toluene or photolysis with a sunlamp rapidly converts a thiohydroxamate ester (32) to the decarboxylated pyridyl sulfide (33). This pyridyl sulfide is formed by addition of an alkyl radical R to the thiohydroxamate (32) followed by fragmentation of (34) as indicated. In the planning of addition reactions by the Barton method, it is usually assumed that the addition step 1 is rate limiting. However, there is now evidence that step 1 may sometimes be reversible and step 2 may be rate limiting.153... 

The lithiated dimethoxybenzene reaction with 2,2-dipyridyl disulfide produced 2,5-dimethoxyphenyl 2-pyridyl sulfide which distilled at 135-150 °C at 0.4 mm/Hg and could be recrystallized from cyclohexane containing 2% EtOH to give aproduct thatmelted at 66-67.5 °C. Anal. (CnHnNO,S) C,H. This would have produced 2,5-dimethoxy-4-(2-pyridylthio)phenethylamine (2C-T-10) but it was never pursued. 

Dienes from ally lie 2-pyridyl sulfides. Treatment of the carbanion of the 2-pyridyl sulfide 2 with tri- -butyl(iodomethyl)tin (1) results in formation of 1-phenylbutadiene (3) directly. 

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