Sulfides from thiols + alkenes

Sulfides, or thioethers, are sulfur analogues of ethers, and like ethers they can be either symmetrical (R2S) or unsymmetrical (RSR1, where R and R are different). Sulfides can be prepared from alkyl halides by a Williamson-type synthesis with sodium hydrogen sulfide, sodium thiolate or sodium sulfide from alkyl or aryl halides via the Grignard reagent (11) from alkenes by radical-catalysed addition of thiols or by reduction of sulfoxides (Scheme 9).2b... 

The main by-products of this synthesis type are sulfides and the isomer resulting from the Markownikoff addition to the alkene. For example, in the synthesis of 1-butanethiol (eq. 4), 5-thianonane, C H SC H, and 2-butanethiol are produced as by-products. The 2-butanethiol has uses as a herbicide intermediate and a gas odorant blend component and is further processed. The 5-thianonane is incinerated or reprocessed for fuel value. Sulfides account for up to 10% of the thiols produced. Another 2—5% is the Markownikoff addition product. 

Several thiols occur naturally for example, skunk secretion contains 3-methyll-butanethiol and cut onions evolve 1-propanethiol, and the thiol group of the natural amino acid cysteine plays a vital role in the biochemistry of proteins and enzymes (see Introduction, p. 2). Primary and secondary thiols may be prepared from alkyl halides (RX) by reaction with excess sodium thiolate (SN2 nucleophilic substitution by HST) or via the Grignard reagent and reaction with sulfur. Tertiary thiols can be obtained in good yields by addition of hydrogen sulfide to a suitable alkene. Thiols can also be prepared by reduction of sulfonyl chlorides (Scheme l).la,2a... 

Hart assembled olefin 109 convergently from benzyl bromide 106 by taking advantage of the Ramberg-Backlund reaction.59 As depicted below, the Sn2 displacement of benzyl bromide 106 with thiol 107 led to sulfide 108. Oxidation of 108 to the sulfone, followed by the Myers modification delivered alkene 109, an intermediate for the synthesis of C-aryl glycosides related to chrysomycins. 

As with all catalysts, palladium and its alloys are susceptible to poisoning [69]. Catalysts must be designed with resistance to poisoning, and proper precautions must be taken to minimize exposure of the membranes to catalyst poisons [69]. Typical poisons for palladium include H2S and other compounds of sulfur such as carbon disulfide (CS2), carbonyl sulfide (COS), aromatic thiophenes and mercap-tans (thiols, R-SH). Palladium is poisoned by the Group VA elements, P, As, Sb and Bi, the halides (Cl, Br, I), and Si, Pb and Hg. Alkenes and unsaturated organic compounds can poison palladium as can elemental carbon deposited from decomposition of carbonaceous materials. Carbon monoxide in high concentrations and at low temperatures can form a monolayer which blocks adsorption and dissociation of molecular hydrogen. Carbon monoxide can also decompose to produce car-... 

Sulfur-containing compounds (thiols and sulfides) are easily recognized from the M -h 2 isotopic peak each sulfur contributes 4.4% to the abundance of the M -I- 2 ion. The fragmentation patterns of thiols (mercaptans) and sulfides (thioethers) parallel the corresponding alcohols and ethers. For example, similar to the alcohol series at m/z 31,45, 59,..., the a-cleavage in thiols produces a series of ions at m/z 47, 61, 75, 89,..., and each ion has a satellite peak 2 u higher, due to In addition, thiols exhibit a characteristic loss of H2S, followed by the elimination of alkene moieties to produce peaks at (M — 34)+, (M — 34 — 2114)+, and so on. In contrast, secondary thiols show a characteristic peak at (M — SH)+. Aromatic thiols also behave similarly to phenols under El conditions. In addition, they show ions at (M — S)+, (M — SH)+, and (M — 2114)+. ... 

The resulting thiolate anion is then capable of displacing halogen from a second equivalent of alkyl halide. This produces the corresponding thioether (dibutyl sulfide, Equation 8.59). In practice, thiol synthesis via the Sn2 process is best undertaken using a large excess of hydrosulfide anion so that the relative concentration of thiolate anion is minimized and thioether formation (Equation 8.59) is repressed. However, even under the best of circumstances, elimination competes with substitution. Alkenes can even be the major product and with tertiary alkyl halides, it is common to find that only alkenes result. 

A similar Nicolas-Pauson-Khand combination was used in a synthesis of the ketone analogue of biotin 7.98, required for biochemical studies (Scheme 7.25). In this case, the Nicholas reaction was intermolecular, between allyl thiol as the nucleophile and carbocation 7.94 generated from alcohol 7.93. The Pauson-Khand reaction was then between the dicobalt complexed alkyne 7.95 and the double bond from the thiol moiety. The Pauson-Khand reaction proceeded with no stereoselectivity, and the diastereoisomers had to be chromatographically separated at a later stage. The synthesis was completed by reduction of the alkene of cyclopentenone 7.96, without using palladium-catalysed hydrogenation due to the sulfide moiety, and ester hydrolysis. 

Fragmentation Loss of alkyl radicals by cleavage of the C-C bond next to S (the largest group being lost preferably) and of the C-S bond, followed by alkene and H2S elimination. Alkene elimination from M " to form the corresponding thiol ions. In contrast to thiols and cyclic sulfides, no H2S or HS elimination from M+-. 

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