Oxidative desulfurization reaction scheme

The kinetics of the oxidation of l-phenyl-2-thiourea by chlorite, in aqueous acidic media, are strongly influenced by the pH and show a complex acid dependence. The proposed mechanism involves HOC1 as a major intermediate whose autocatalytic production determines the observed kinetics of the reaction. The oxidation involved the formation of two stable intermediates, the sulfinic acid and the sulfonic acid, on the pathway towards total desulfurization to form phenylurea. A comprehensive 29-reaction scheme has been proposed to describe the observed complex kinetics.96 The oxidation of trimethylthiourea (TMTU) by chlorite in slightly acidic media is very fast. The oxidation of TMTU proceeds through the formation of sulfinic acid then to the sulfoxylate anion. The direct reaction of chlorine dioxide and TMTU is autocatalytic and is also inhibited by acid. A series of 28 reactions have been proposed to describe the mechanism.97... 

In what is effectively a desulfurization reaction, 1,2-dithiolane 1,1-dioxide reacts exothermically with aminophosphines such as tris(diethylamino)phosphine in benzene solution to give 1,2-oxathiolane 1-oxide in excellent yield (71JOC322). The reaction, which requires a slight excess of the aminophosphine, is shown in Scheme 41. 

Oxidative desulfurization can be effected by ozonolysis (Scheme 74). 2-Thiol-4(3//)-quinazolinone on ozonolysis in dry dichloromethane yields the disulfide (448) which is resistant to further oxidation under the reaction conditions. In acetic acid, desulfurization results with hydrogen substitution (449). Rationalization of the reaction in acetic acid involves formation of an unstable sulfinic acid which loses SO2 with replacement by hydrogen. In dichloromethane containing ethanol, the 2-ethoxy product (450) formed, corresponding to nucleophilic substitution of the reactive sulfinic acid from the oxidation. Similarly, ozonolysis of pyrimidine-2-thione acid gave bis-2-pyrimidinyl disulfide in dry dichloromethane and 2-ethoxypyrimidine in the presence of ethanol <93TL1631>. 

Treatment of 3-amino-5,6-dihydro-2-thioxo-l,3-thiazin-4(3//)-ones (75) with nitrous acid results in oxidative desulfurization and the formation of the corresponding diones (76). However, if the N-amino substituent bears two methyl groups the reaction can proceed further and monodemethylation and 7V-nitrosation may take place, leading to the nitrosamine (77) (Scheme 9) <86AP521>. 

In the base-induced conversion of pyridinium salts (199) to pyrazolo[l,5-a]pyridines, 4,4a-di-hydropyrido[l,2-t ][l,3,4]thiadiazine intermediates (200) could be identified by H NMR, but were not isolable. Their subsequent oxidation may afford 127t antiaromatic systems (201) which upon disrotatory cyclization to tricyclic thiiranes (202), followed by desulfurization or acyl migration, gave differently substituted pyrazolo[l,5-a]pyridines, (203) and (204), respectively (Scheme 14) <85BCJ1432,84H(22)2237>. A similar desulfurization reaction of this ring system has also been reported <73CPB2146>. 

The oxidants used in this reaction are hydrogen peroxide, peracids or organic peroxides, but the high cost of H2O2 or organic hydroperoxides makes the economics unfavourable in comparison with the traditional hydro-desulfurization process. In order to overcome this limitation, Eni/UOP jointly developed a new oxidative desulfurization process in which the hydroperoxide is directly produced in the reaction medium and in this way ULSD production can become economically convenient. A concept scheme of the process is given in Fig. 15.8. 

Reaction of the bicyclic 1,3,4-oxadithiolane (113) with triphenylphosphine in refluxing toluene led to an equilibrium mixture of the 1,3-oxathietane (114) and the thiocarbonyl derivative (115) (Scheme 29) <93BCJ1714>. Raney nickel can be used to desulfurize both 1,2,4-trithiolanes (to methylene compounds) and 5,5-disubstituted 1,2,4-oxadithiolane 2-oxides (116) which give rise to secondary alcohols (Equation (20)) <90BSB265>. 

Wynberg and Feijen studied thieno[3,4-6]thiophene (3) formylation and found that both positions 4 and 6 are attacked. This is in accordance with theoretical predictions. The reaction produces a mixture (7 3) of 4-formyl- (194) and 6-formylthieno[3,4-6]thiophene (195) in 56% total yield after separation and purification. The formyl derivatives obtained were oxidized to the corresponding carboxylic acids 196 and 197, which were converted into 3-ethylpentanoic 198 and 4-methylhexanoic (199) acids by desulfurization with Raney nickel [Scheme 15]. 

Scheme 1.64). The Ag(I)-mediated cyclization afforded dipole 306 for 1,3-dipolar cycloaddition with methyl vinyl ketone to yield adducts 307 and the C(2) epimer as a 1 1 mixture (48%). Hydrogenolytic N—O cleavage and simultaneous intramolecular reductive amination of the pendant ketone of the former dipolarophile afforded a mixture of alcohol 308 and the C(6) epimer. Oxidation to a single ketone was followed by carbonyl removal by conversion to the dithiolane and desulfurization with Raney nickel to afford the target compound 305 (299). By this methodology, a seven-membered nitrone (309) was prepared for a dipolar cycloaddition reaction with Al-methyl maleimide or styrene (301). 

Reaction of thieno[3,4-6]thiophene (8) with DMF/POCl3 gave a 7 3 mixture of C-4 and C-6 formyl derivatives (58) and (59), respectively (76AHC(19)123). The substitution pattern was ascertained by oxidation to the carboxylic acids (60) and (61) and subsequent reductive desulfurization. The C-4 substituted isomer (60) yielded 3-ethylpentanoic acid (62) while the C-6 isomer led to 4-methylhexanoic acid (63 Scheme 14). 

Thiane oxides have been shown to be reduced cleanly back to the thiane with phosphorus pentasulfide under conditions to which sulfones, sulfinates, ketones, esters and amides are inert (78CJC1423) the potential of this reaction, though not yet applied, is obviously considerable, especially when coupled with the old-established Raney nickel desulfurization technique. Thiane itself is desulfurized to pentane (with traces of cyclopentane) but the opportunity to construct alkyl chains of great complexity regio- and stereo-specifically is there. At the very least, the reduction to tetrahydrothiopyrans presents a very useful entree into a wide range of 2-substituted thianes (Scheme 2). 

Oxidation of 6,ll-diethyl[l,4]dithiino[5,6- ]benzopentathiepin 35 by a Sharpless reagent [Ti(0-i-Pr)4// ,/ -DET/ /-BuOOH] produced optically active 4,9-diethyl[ l,4]-dithiino[5,6-/]bcnzo[ l, 2,3]trithiole-5-oxidc 36 (Scheme 4). The reaction was accompanied by desulfurization and ring contraction of the pentathiepin ring <2003HAC88>. 

In a recent pubhcation the nitrile (EWG = CN) variant [ 126] of this chemistry was performed in water by applying N,N-diethylaminopropylated sihca gel as heterogeneous catalyst [ 128]. Another variant of this reaction sequence, leading to chiral sulfinylated enones, has been developed by Llera [ 129] employing the enantiomerically pure geminal bis(sulfoxide) 208 (Scheme 54). This bis(sulfoxide) was prepared from (-)-p-toluenesulfinic acid menthyl ester [100], as described by Kunieda [130]. Later this procedure was improved to increase the yield from 35 to 91% [13,131]. Treatment of 208 with enolizable aldehydes or ketones, in the presence of piperidine as a base and thiophile, initiated a reaction cascade involving a condensation step (to 210), a proton shift to allylic sulfoxide 211, and a [2,3]-0-shift followed by a piperidine-mediated desulfuration delivering the alcohols 212 as isomeric mixtures. Oxidation of the latter compounds (one of the R = H) led to enantiomerically pure E-y-oxo vinyl sulfoxides 213. 

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