Protons on Sulfur

Sulfhydryl protons usually exchange at a low rate so that at room temperature they are coupled to protons on adjacent carbon atoms (7—8 Hz). They do not exchange rapidly with hydroxyl, carboxylic, or enolic protons on the same or on other molecules thus, separate peaks are seen. However, exchange is rapid enough that shaking the solution for a few minutes with deuterium oxide replaces sulfhydryl protons with deuterium. The absorption range for aliphatic sulfhydryl protons is 81.6 to 8 1.2 for aromatic sulfhydryl protons, 8 3.6 to 8 2.8. Concentration, solvent, and temperature affect the position within these ranges. 

---

A mechanism analogous in many ways to that of the acid-catalyzed ring opening reaction was advanced for the reaction of the thiirane oxide with alkyl chloromethyl ethers S . The first step is the displacement of the chloride by the sulfoxy oxygen (equation 24). In view of the above mechanistic interpretation, it is quite surprising that the parent thiirane oxide (16a) was found to be protonated on sulfur and not at oxygen in FSOjH-SbFfi at — 78 °C, according to NMR studies s . 

O-protected cyclic or acyclic carbon frameworks. The choice of acetals or ethers as derivatives allows a systematic manipulation of diols and polyols. Kinetic control and a lesser affinity for protonation on sulfur compared with oxygen allows the transformation of cyclic hemiacetals into acyclic dialkyl dithioacetals. Acetal, ether, and dithioacetal derivatives are some of the pivotal intermediates needed to explore various applications of carbohydrates in synthesis. 

Sulfur as Heteroatom. Thiols and sulfides are protonated on sulfur in superacid media and give mono- and dialkylsulfonium ions, respectively.136 Thio-carboxylic acids, 5-alkyl esters, thioesters, dithioesters, and thiocarbonates in similar media also form stable protonated ions541,647 such as cations 348-353. 

Secondary Sulfonium Ions. Protonated aliphatic sulfides have been studied at low temperatures by NMR spectroscopy in strong acid systems149 [Eq. (4.38)]. They show well-resolved NMR spectra, with the proton on sulfur being observed at about 81 H 6.0. 

The NMR spectrum of protonated thiane-3,3,5,5-c/ has also been studied in HS03F-SbF5 to determine the conformational position of the proton on sulfur in the six-membered ring and to study the ring inversion process.162 The proton on sulfur resides exclusively in the axial position. 

In a further development on this theme, the thiol, 153, is first alkylated to the corresponding benzyl ether (158). Treatment with sodium methoxide removes the proton on the amide nitrogen to afford the ambient anion (159). This undergoes alkylation with methyl bromide on the ring nitrogen thus it locks amide into the imine form (160). Chlorolysis serves both to oxidize the sulfur to the sulfone stage and to cleave the benzyl ether linkage there is thus obtained the sulfonyl chloride, 161. 

Of the several syntheses available for the phenothiazine ring system, perhaps the simplest is the sulfuration reaction. This consists of treating the corresponding diphenylamine with a mixture of sulfur and iodine to afford directly the desired heterocycle. Since the proton on the nitrogen of the resultant molecule is but weakly acidic, strong bases are required to form the corresponding anion in order to carry out subsequent alkylation reactions. In practice such diverse bases as ethylmagnesium bromide, sodium amide, and sodium hydride have all been used. Alkylation with (chloroethyl)diethylamine affords diethazine (1), a compound that exhibits both antihista-minic and antiParkinsonian activity. Substitution of w-(2-chloroethyl)pyrrolidine in this sequence leads to pyrathiazine (2), an antihistamine of moderate potency. 

Several studies338,340-342 show that the chlorination does not proceed, as assumed previously343, by proton abstraction followed by reaction of the carbanion thus formed, with electrophilic chlorine. A mechanism involving a chlorooxosulfonium ion formed by attack of a positive chlorine species on sulfur was shown to be more likely344. 

The first step consists in the attack of a proton on the W-H bond to yield a labile dihydrogen intermediate (Eq. (3)) that rapidly releases H2 to form a coordi-natively unsaturated complex (Eq. (4)). This complex adds water in the next step to form an aqua complex (Eq. (5)) that completes the reaction by substituting the coordinated water by the X anion (Eq. (6)). Steps (3)-(6) are repeated for each W-H bond and the factor of 3 in the rate constants appears as a consequence of the statistical kinetics at the three metal centers. The rate constants for both the initial attack by the acid (ki) and water attack to the coordinatively unsaturated intermediate (k2) are faster in the sulfur complex, whereas the substitution of coordinated water (k3) is faster for the selenium compound. 

Initial attempts to spread the amide as a monolayer film on aqueous subphases failed. Since patches of microcrystals could be observed by careful inspection, it was concluded that the aggregation forces in the sohd phase were too great to permit significant expansion of the molecules onto the adjacent surface of the air-water interface. It is well known that amides are weak bases that are protonated on the carbonyl oxygen by moderately strong aqueous acid. Accordingly, a series of subphases prepared from carefully purified sulfuric acid-... 

As observed, aromatic hydrocarbons gave products of protonation on dissolution in hydrofluoric acid. Oxidation into aromatic cation-radicals did not take place (Kon and Blois 1958). Trifluoro-acetic acid is able to transform aromatics into cation-radicals. This acid is considered a middle-powered one-electron oxidant (Eberson and Radnor 1991). Its oxidative ability can be enhanced in the presence of lead tetraacetate. This mixture, however, should be used carefully to avoid oxidation deeper than the one-electron removal. Thus, oxidation of 1,2-phenylenediamine by the system Pb(OCOCH3)4 -I- CE3COOH -P CH2CI2 leads to the formation of either primary or secondary cation-radicals. The primary product is the cation radical of initial phenylenediamine, whereas the secondary product is the cation radical of dihydrophenazine (Omelka et al. 2001). Sulfuric acid is also used as an one-electron oxidant, especially for aromatic hydrocarbons. In this case, generation of cation radicals proceeds simultaneously with the hydrocarbon protonation and sulfonation (Weissmann et al. 1957). 

---