Sulfoxides reaction with acetic anhydride

Thermolysis of trithiane (69) or carbonate (70) at reduced pressure yields methylene-thiirane which is stable in cold, dilute solution (Scheme 152) (78JA7436, 78RTC214). A novel acenaphthylene episulfide is obtained by treatment of the six-membered sulfoxide (71) with acetic anhydride (Scheme 153) (68JA1676), and photolysis of (72) gives a low yield of episulfide (73 Scheme 154) (72JA521). Low yields may be due to the desulfurization of the thiiranes under the reaction conditions. 

Compound 264 is unexpectedly stable against light, but can easily be oxidized to the sulfoxide 265 and the sulfone 266. Sulfoxide 265 can be isolated and a-activated by reaction with acetic anhydride (Scheme 4.46). a-Acetoxylated tetrahydrothio-phene 267 has 0,S-acetal-like reactivity and can be functionalized with various alcohols or thiols under acid catalysis with camphorsulfonic acid (CSA) (268). 

There is no easy and/or effective method for the preparation of 1,2,3,4-tetrasubstituted naphthalenes starting from a simple naphthalene derivative and based on classical substitution methodology. A clever new route, based on the now common concept of "tandem" reactions, is illustrated as follows. Heating of the sulfoxide 1 with acetic anhydride at 120°C in the presence of maleic anhydride gave an adduct 2, C20H16O4S, in 87% yield as a mixture of diastereomers. Reaction of the adduct 2 with PTSA in THF at 25°C gave the naphthalene derivative 3 in quantitative yield. Use of methyl propiolate in place of maleic anhydride did not result in isolation of an adduct the product was the tetralone 4 (51%). 

The oxidation of diols having alcoholic groups of the same nature, for example, both alcoholic groups are primary, secondary, allylic, or benzylic, is usually carried out at both groups to yield dialdehydes [832] or diketones [552], Such reactions are achieved by chromium trioxide [582], barium manganate [832], dimethyl sulfoxide activated with acetic anhydride [1013], and others (equations 284 and 285). 

Vinyl sulfides are prepared from sulfoxides under a variety of conditions. These include reaction with acetic anhydride at reflux, with trifluoroacetic anhydride in the presence of an amine base and with acetic anhydride in the presence of an acid catalyst. In fact, precautions must be taken in certain Pum-merer reactions discussed in the preceding sections to avoid competing vinyl sulfide formation. 

In the reaction of sulfoxide (144) with acetic anhydride the available evidence points to the formaticHi of the disulfide dication intermediate (145) and subsequent rate-determining loss of a benzylic proton to give (14(>a pathway d Scheme 35). On the basis of experiments conducted on related substrates the alternative mechanism involving the formation of the quinidomethide intermediate (146b) was ruled out. 

A Pummerer-initiated cascade reaction has also been used as a method for generating isomiinchnones for further use in cycloaddition chemistry. For example, treatment of sulfoxide 23 with acetic anhydride first resulted in the formation of a reactive thionium ion that reacted with the distal amide carbonyl group to produce isomunchnone 24 (Scheme 6) (99JOC2038). Exposure of 24 to a dipolarophile, such as iV-phenylmaleimide, resulted in 1,3-dipolar cycloaddition to give 25 as a single diastereomer in 85% yield. 

Benzoxathiin and benzodithiin derivatives can also be derived as rearrangement products of other heterocyclic rings. Thus, nonstereospecific ring expansion reactions of 1,3-benzoxathiole sulfoxides (210) and 1,3-benzodithiole sulfoxides (211) with acetic anhydride or /j-toluenesulfonic acid afford the corresponding 1,4-benzoxathiins or 1,4-benzodithiins (212) and (213) in satisfactory yields... 

The Pummerer rearrangement was reported by Rudolf Pummerer in 1909 when he published a paper in Chemische Berichte. Earlier in the same year, Smythe had reported the reaction of dibenzyl sulfoxide 3 with acetic anhydride and hydrochloric acid to give benzaldehyde 4 and thioacetal 5, among other products. Smythe was apparently unable to explain the product distribution, which was then left to Pummerer do so in his much-cited paper later that year. Pummerer published the reaction of sulfinyl acetic acid 6 with hydrochloric acid to give glyoxylic acid 7. The formal oxidation of the... 

Pummerer wrote only one further paper on this chemistry, in 1910. The reaction of sulfoxide 11 with acetic anhydride was shown to afford sulfide 12 in what is now recognised as the classical Pummerer rearrangement. From these two reports, the scope of the Pummerer rearrangement has been investigated by many prominent groups who have spent much time and effort in extending the utility of this illustrious reaction. This is perhaps best exemplified by the considerable number of reviews on the Pummerer rearrangement. " ... 

Pummerer Reaction. In 1910, Pummerer reported that sulfoxides react with acetic anhydride to give 2-acetoxy sulfides (eq 21). The sulfoxide must have one a-hydrogen. Alternative reaction conditions include using trifluoroacetic anhydride and acetic anhydride. 

Low DS starch acetates ate manufactured by treatment of native starch with acetic acid or acetic anhydride, either alone or in pyridine or aqueous alkaline solution. Dimethyl sulfoxide may be used as a cosolvent with acetic anhydride to make low DS starch acetates ketene or vinyl acetate have also been employed. Commercially, acetic anhydride-aqueous alkaU is employed at pH 7—11 and room temperature to give a DS of 0.5. High DS starch acetates ate prepared by the methods previously detailed for low DS acetates, but with longer reaction time. 

Due to their thermal instability, this method cannot be applied to the preparation of benzo-thiepins. Although the ft-oxo sulfoxide moiety in precursors such as 5-methoxy-4-phenyl-l-benzothiepin-3(2/7)-one 1-oxide makes them candidates for a Pummerer reaction, treatment with acetic anhydride and triethylamine at - 30 C results in preferential enol acetylation to afford the corresponding 1-benzothiepin 1-oxide.14... 

The Pummerer reaction of conformationally rigid 4-aryl-substituted thiane oxides with acetic anhydride was either stereoselective or stereospecific, and the rearrangement is mainly intermolecular, while the rate-determining step appears to be the E2 1,2-elimination of acetic acid from the acetoxysulfonium intermediates formed in the initial acetylation of the sulfoxide. The thermodynamically controlled product is the axial acetoxy isomer, while the kinetically controlled product is the equatorial isomer that is preferentially formed due to the facile access of the acetate to the equatorial position . The overall mechanism is illustrated in equation 129. 

A stereoselective Pummerer reaction was first observed with the diastereomeric cyclic sulfoxides 269. It was found (299) that when the CIS- or tra 5-sulfoxides 269 are heated for several hours with acetic anhydride, the corresponding cis- or fraws-acetoxysulfides 270 are formed with a stereospecificity exceeding 85%. 

Continuing their search for ways to synthesize this system. Cava and Husbands " allowed tetrabenzoylethane (146) to react with phosphorus pentasulfide in refluxing xylene to obtain 46% of 1,3,4,6-tetraphenyl-li/,3if-thieno[3,4-c]thiophene (147) oxidized with periodate the latter yielded the sulfoxide (148), which was dehydrated with acetic anhydride to produce the stable l,3,4,6-tetraphenylthieno[3,4-c]thiophene (149) (87%). The latter is obtained in one step, in about 3% yield, by the reaction of tetrabenzoylethane (146) with phosphorus pentasulfide in refluxing xylene, along with the formation of 147 (30%). A mixture of two ad-... 

An unusual dehydration reaction was observed in the case of sulfoxide 290, which yielded 99% of 2//-thiopyran 291 on heating with acetic anhydride.302... 

These various intermolecular a-acetoxylation reactions have intramolecular counterparts. For example, treatment of the sulfinylbutanoic acid shown in equation (11) with acetic anhydride containing p-toluenesulfonic acid yields a sulfenylated butanolide, the carboxylic acid function having intercepted the a-thiocarbocation intermediate. Yet another demonstration of Ae intramolecular process, due to Al-lenmark, is the cyclization of o-carboxyphenyl benzyl sulfoxide with acetic anhydride to form the 1,3-benzoxathian-4-one shown in equation (12). This reaction was also conducted with one of the... 

The Pummerer reaction of optically active R)- +)-a-(p-tolylsulfinyl)-A/,Al-dimethylacetamide with Acetic Anhydride in the presence of 1,3-Dicyclohexylcarbodiimide is highly stereoselective, affording the corresponding a-acetoxy sulfide in moderate yield but with nearly 70% ee (eq 2). The recovered starting sulfoxide is obtained in 63% yield. 

Protection of aldoses at the non-anomeric positions makes it possible to use many of the common procedures in organic chemistry for oxidizing lactols as shown with mannofura-nose 1 and glucopyranose 3 (O Table 1). The reactions can be divided into three main categories oxidations mediated by activated dimethyl sulfoxide (DMSO), oxidations with chromi-um(VI) oxides, and oxidations catalyzed by ruthenium oxides. The DMSO-mediated oxidations of alcohols can be promoted by several activators [27]. With the partially protected aldoses the activation has mainly been achieved with acetic anhydride and oxalyl chloride. Competing /3-elimination does usually not occur unless the eliminating group is an ester, e. g., an acetate or a benzoate [27]. 

In this class of Pummerer reactions subsequent formation of the a-acyloxy sulflde involves, in the majority of instances, an intermolecular acyloxy migration. The reaction of p-tolyl benzyl sulfoxide with acetic anhydride is an exception. However, even in this case no asymmetric induction is observed. ... 

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