Thio-ethers

Ullman reaction The synthesis of diaryls by the condensation of aromatic halides with themselves or other aromatic halides, with the concomitant removal of halogens by a metal, e.g. copper powder thus bromobenzene gives diphenyl. The reaction may be extended to the preparation of diaryl ethers and diaryl thio-ethers by coupling a metal phenolate with an aryl halide. 

Sulfides orthio derivatives Metallic derivatives of thio ethers and disulfides, usually mixed with organic phosphite esters long-chain alkyl thienyl ketones Lubricating oils boiler water... 

Nearly every substitution of the aromatic ring has been tolerated for the cyclization step using thermal conditions, while acid-promoted conditions limited the functionality utilized. Substituents included halogens, esters, nitriles, nitro, thio-ethers, tertiary amines, alkyl, ethers, acetates, ketals, and amides. Primary and secondary amines are not well tolerated and poor yield resulted in the cyclization containing a free phenol. The Gould-Jacobs reaction has been applied to heterocycles attached and fused to the aniline. 

Sjwyer and coworkers have developed an efficient alternative UUmann synthesis of diaryl ethers, diaryl thioethers, and diarylamines using the SnAt reaction. Phenol, thiophenol, or aniline reacts v/ith an appropriate aryl halide, In the presence of KF-aliunina and 18-crovm-6 In acetonitrile or DMSO to give the corresponding diaryl ether or diaryl thio ether as shovm In Eqs. 9.6 and 9.7. ... 

Thio-ameisensiiure, /. thioformic acid, -anti-monsaure, /. thioantimonic acid, -arsenig-saure, /. thioarsenious acid, -arsenaaure, /. thioarsenic acid, -ather, m. thio ether, -car-baminsaure,/. thiocarbamic acid. 

The present method of preparing 2-cyclohexyloxyethanol has been described before,6 but on a smaller scale. Other /3-hydroxy ethers6 and /3-hydroxy thio ethers 8 can be prepared by the same method. Hydrogenolysis of the C—O bond in acetals has also been reported7 with diisobutylaluminum hydride for example, 2-cyclohexyloxyethanol was obtained in 91% yield in this manner. 

Table 2.2 Selected mutant CHMOs from Adnetohacter sp. NCIMB 9871 for the enantioselective air-oxidation of thio-ether 40 (24 hours 23-25 °C) using whole cells [32].

Ethylidenetriphenylphosphorane and iV-methyl-iV-phenylthioacetamide (89) in THF gave a suspension from which the vinyl thio-ethers (91) were obtained on treatment with carbonyl compounds. The suspension... 

Among phosphonate esters (170) used in olefin synthesis were those with R = S-CeHi-Br-/ , S02 C6H4-Br-A CO-NHR, and S CHa CEi-XHa. The allyl vinyl thio-ethers (171) obtained using the last of these gave a-allyl-aldehydes on pyrolysis in the presence of red mercuric oxide. 

The phycobiliproteins are accessory photosynthetic pigments aggregated in cells as phycobilisomes that are attached to the thylakoid membrane of the chloroplast. The red phycobiliproteins (phycoerythrin) and the blue phycobiliprotein (phycocy-anin) are soluble in water and can serve as natural colorants in foods, cosmetics, and pharmaceuticals. Chemically, the phycobiliproteins are built from chro-mophores — bilins — that are open-chain tetrapyrroles covalently linked via thio-ether bonds to an apoprotein. ... 

When the pH of ribonuclease was raised to 8.0 from 5.5 a second site became partially occupied in which the platinum bound to histidine 119. At the lower pH this group would be protonated and blocked. As stated above for this reason groups such as terminal —NH2, arginines and lysines are not likely to be as effective as thio-ether in displacing chloride from chloride complexes of platinum. (We are grateful to Dr. L. Johnson (Oxford) for supplying us with much of this information). 

The cleavage of thio-ethers suggested that the breakdown of the ylide derived from the reaction of an aryne with tetrahydrothiophen... 

There has been significant emphasis on the use of pyrimidine thio ethers for further selective functionalisation by nucleophilic displacements of either the alkylthio or alkylsulfone and general syntheses of pyrimidines often include methylthio as one of the representative substituents. 

Et3SiH/TFA reduces disulfides to the corresponding mercaptans in modest yields (Eq. 340).564 Naphthyl thio ethers are reduced in rather poor yields to tetrahydronaphthalene with the combination EtjSiH/HF -OfE (Eq. 341).263 There is one report of the reduction of a diaryl sulfide to the hydrocarbon but the yield... 

Formation of ring-substituted arylamine thio ethers occurs also by proton-catalyzed thermal rearrangement of the corresponding sulfenamides73,82,83. This alternative pathway may not completely be excluded in thio ether formation from nitrosoarenes, but it seems unlikely since these thio ethers were produced at neutral pH and low temperatures68. The discovery of the fc -conjugate additionally favors the pathway of nucleophilic ring addition of thiolate to the sulfenamide cation. 

Hitherto, thio ether formation has clearly been proved only in the case of the ji-donor substituted 4-nitrosophenetol and the electron-rich l-methyl-2-nitrosoimidazole. The low yields of this adduct (about 2% at 1 1- and about 10% at 1 5-stoichiometry for 4-nitrosophenetol reacting with GSH56) may be the reason for its rare discovery. However, other nitrosoarenes should yield this family, too. Semiempirical molecular orbital calculations (MNDO) indicate a similar positive charge at the exposition of the N-(methylthiol-S -yl)-aniline cation and -4-anisole cation as well (Scheme 6). Furthermore, formation of l-(glutathion-S -yl)-2-naphthylamine was reported to occur in mixtures of 2-nitrosonaphthalene and GSH12. 

Misonidazole [27 l-methoxy-3-(2-nitroimidazol-l-yl)-2-propanol] and the model compound l-methyl-2-nitroimidazole have been used as radiosensitizers in the treatment of certain types of human tumors. One important property of these compounds is that they are more toxic to hypoxic cells than to aerobic cells, indicating that reductive metabolism of the drug is involved in the toxicity. Results of a number of studies suggest that intracellular thiols play a significant role in the hypoxic cell toxicity, and it was found that reduction products formed stable thio ethers with GSH (for literature see References 181-183). The reaction mechanism of thio ether formation has not been fully established. It has been suggested that the 4-electron reduction product was involved in thio ether formation181,184,185, and that the hydroxylamine rather than the nitroso derivative was the reactant. On the other hand, an intermediate nitroso derivative is expected to give a sulfenamide cation (see Scheme 1) which easily allows thio ether formation. 

When 1-methyl-2-nitrosoimidazole became available190 it was found that addition of excess GSH to solutions of l-methyl-2-nitrosoimidazole led to a rapid loss of the characteristic absorbance at 360 mn within a few seconds. Preliminary experiments suggested that formation of GSSG and the hydroxylamine was followed by formation of stable thio ethers. It should be noted, however, that detection of free hydroxylamine was unsuccessful57. In cell-free systems l-methyl-2-nitrosoimidazole reacted with excess GSH to form adducts in a 1 3 stoichiometric reaction191. 

Mark6 and colleagues178 studied the Eu(hfc)3 catalyzed inverse electron demand Diels-Alder reactions between (—)-pantolactone derived chiral a-pyrones 279 and vinyl ethers and thio ethers 280. This auxiliary proved superior to other auxiliaries in these reactions. The reactions generally proceeded with high yields, affording the endo adducts 281 with de values generally above 95%. The de proved independent of the chirality or achirality of the Lewis acid employed, as (+)-Eu(hfc)3, (—)-Eu(hfc)3 and Eu(fod)3 all afforded the same diastereomer with >95% de (equation 78, Table 13). 

Oxidation reactions using mediators are possible under very mild conditions with high selectivity. In fact, the oxidative cleavage of the carbon-sulfur bond of thio ether (16) was easily possible by using mediator (17) (Scheme 6) [46]. 

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