Preparation of Sulfones

Aromatic nucleophilic substitution of 2- or 5-halogenotltia20les (146 and 148) by sulfinate affoiMs an alternative method of preparation of sulfones (147 and 149) (Scheme 76) (170, 354-356). 

Numerous other penicillin sulfones have been reported to be P-lactamase inhibitors, as illustrated in Table 5. The effect of C-6 substituents has been extensively explored starting with 6-APA sulfone (25, R = NH2, R = H, R" = R " = CH ), which has modest activity. Mechanistic considerations led to preparation of sulfones of poor substrates, compounds such as methicillin, cloxaciUin, nafaciUin, and quinaciUin sulfone (25,... 

This ch ter contains reactions which prepare the oxides of nitrogen, sulfur and selenium. Included are W-oxides, nitroso and nitro compounds, nitrile oxides, sulfoxides, selenoxides and sulfones. Oximes are considered to be amines and appear in those sections. Preparation of sulfonic acid derivatives are found in Chapter Two and the preparation of sulfonates in Chapter Ten. 

Trifluoromethanesulfonates of alkyl and allylic alcohols can be prepared by reaction with trifluoromethanesulfonic anhydride in halogenated solvents in the presence of pyridine.3 Since the preparation of sulfonate esters does not disturb the C—O bond, problems of rearrangement or racemization do not arise in the ester formation step. However, sensitive sulfonate esters, such as allylic systems, may be subject to reversible ionization reactions, so appropriate precautions must be taken to ensure structural and stereochemical integrity. Tertiary alkyl sulfonates are neither as easily prepared nor as stable as those from primary and secondary alcohols. Under the standard preparative conditions, tertiary alcohols are likely to be converted to the corresponding alkene. 

A. Cahn, H. Lemaire, R. Haass, Preparation of sulfonated fatty acid ester surface-active agents, US Patent 3 320 292 (1967). 

Nucleophilic phosphinations, Grignard-reactions and catalytic cross-coupling for preparation of sulfonated phosphines... 

A) To demonstrate the variety of procedures available for the preparation of sulfonated poly(aryl ether) membranes (for example,... 

Encouraged by our previous results, we studied the allylation of bifunctional sulfones derived from dialdehydes such as terephthalaldehyde and isophtha-laldehyde (Scheme 3). When the classical conditions for the preparation of sulfones... 

Attack by Carbon. Preparation of Sulfones S- Aryl-de-chlorination... 

Oxidation of sulfides and sulfoxides, as discussed above, and alkylation of sulfinate salts are the most common methods used to obtain sulfones for synthetic purposes [71, 109-113], A hydrogen peroxide-urea-phthalic anhydride system was recently proposed as a mild convenient reagent for the efficient preparation of sulfones from organic sulfides [114]. 

The synthesis and reactivity of tetrazole-5-thiones are considered in Section 6.07.7.5. A preparation of sulfone 304 in two steps from the corresponding tetrazole-5-thione 303 by alkylation and subsequent oxidation has been described (Scheme 38) <2006JOC360>. 

Cephalosporins in the sulfoxide or sulfone oxidation states can easily be obtained by treatment with different oxidants. This sulfur oxidation is usually accomplished for one of the following reasons (1) sulfoxide formation to obtain reactive intermediates for further transformations (2) sulfoxide formation with subsequent reduction in cephems to shift the double bond from position 2 to position 3 (3) preparation of sulfones as /3-lactamase or elastase inhibitors. 

Resins carrying the guanidine function have been patented as catalyst[128] for the preparation of organic disulfides and polysulfides11291 and the preparation of sulfonated olefins.[130]... 

Scheme 2.5 Preparation of sulfonic-acid functionalised ionic liquids...

The procedure described above involves sulfonation in the absence of free sulfuric acid at low temperatures, and avoids the use of an appreciable excess of the sulfonating agent. Similar procedures are generally applicable to the preparation of sulfonic acids which cannot be prepared satisfactorily by the ordinary sul-fonation methods, because they are easily isomerized or sulfonated further by concentrated sulfuric acid. Even compounds which are ordinarily converted directly into disulfonic acids, such as carbazole, 4,4 -dihydroxydiphenylmethane, etc., can be monosulfonated in this way. 

A bromine-initiated method for the preparation of sulfonate-linked aziridines has been developed <2001TL1037>. Treatment of the sulfonamide with r-butylhypochlorite generates the intermediate Wchloramine salt. Reaction of the chloramine with phenyltrimethylammonium bromide (PTAB) provides the sulfonamide-linked aziridine. This method does not provide any improvement in yield relative to either the copper- or rhodium-catalyzed reaction systems. It does however work for the preparation of the bicyclo[5.1.0] system as both the copper- and rhodium-catalyzed reactions give C-H insertion products in this attempt to prepare the larger ring system (entry 6). 

Hydrogen peroxide attacks the sulfur atom in preference to the double bond in allyl phenyl sulfide and allyl benzyl sulfide to give allyl phenyl sulfoxide (64%) and allyl benzyl sulfone (85%), respectively. Olefinic sulfones may also be obtained by dehydrohalogenation of /3-haloalkyl sulfones prepared by this method. Oxidation of sulfides has been utilized in the preparation of sulfones containing other common functional groups such as the amide, tro, amino, and ester groups. 

Complementing the examples shown thus far is a wealth of chemistry capable of affecting the transformation of hydroxyl groups to halides. These include the use of iminoesters (Scheme 6.10) [30] and reagents such as methanesulfonyl chloride, which is commonly employed in the preparation of sulfonate leaving groups [31]. The latter example, highlighted in Scheme 6.21,... 

Sulfonate displacement has been well established as a common method for introducing halogen atoms into carbohydrates. The high reactivity and easy preparation of sulfonic esters contribute to their use in carbohydrate chemistry. Triflate displacements are popular for the preparation of secondary halogenated carbohydrates and often give satisfactory results when mesylates and tosylates fail to give products. 

Preparation of sulfones. p-Toluenesulfonyl chloride is reduced with sodium sulfite and sodium bicarbonate to sodium p-toluenesulfinate, which separates as a solid. A mixture of this with dimethyl sulfate, sodium bicarbonate, and water is refluxed for 20 hrs. and the product, methyl p-tolyl sutfone.is extracted with benzene. 

Ionomers of practical interest have been prepared by two synthetic routes (a) copolymerization of a low level of functionalized monomer with an olefinically unsaturated monomer or (b) direct functionalization of a preformed polymer. Typically, carboxyl containing ionomers are obtained by direct copolymerization of acrylic or methacrylic acid with ethylene, styrene and similar comonomers by free radical copoly-merization. Rees (22) has described the preparation of a number of such copolymers. The resulting copolymer is generally available as the free acid which can be neutralized to the degree desired with metal hydroxides, acetates and similar salts. Recently, Weiss et al.(23-26) have described the preparation of sulfonated ionomers by copolymerization of sodium styrene sulfonate with butadiene or styrene. 

The second route to ionomers Involves modification of a preformed polymer. Sulfonation of EPDM, for example, permits the preparation of sulfonated-EPDM with a level of sulfonate groups in proportion to the amount of sulfonating agent(27). These reactions are conducted in homogeneous solutions permitting the direct neutralization of the acid functionality to the desired level. Isolation of the neutralized ionomer is effected by conventional polymer isolation techniques, such as coagulation in a nonsolvent or solvent flashing. These procedures are detailed in several patents and publications(28-31). 

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