Sulfinic acids derivatives

Reaction of a sulfinyl sulfone with a nucleophile in the manner shown in (139) is, of course, an example of a nucleophilic substitution at sulfinyl sulfur. Reactions of this general type occur frequently and are of great importance in the chemistry of most kinds of sulfinic acid derivatives. At this point it would seem desirable to discuss what is known about such key aspects of their mechansim as stereochemistry and the timing of the bond-making and bond-breaking processes necessary in such a substitution. In doing this we will call upon results obtained from the study of such reactions using a variety of different types of sulfinic acid derivatives. 

The chlorosulfite method, which is claimed to be indicated for the synthesis of alkanesulfmates, works only in the case of methanesulfinate. The levels of control of diastereomeric excess with arylzinc and any arylmetal were in general very low. Additionally, reaction of chlorosulfite esters with alcohols and amines produced sulfinic acid derivatives in good yield but with low selectivity (< 2 1). 

Rearrangement of furazan derivatives were studied by Boschi and coauthors [67]. 4-Phenyl-1,2,5-oxadiazole sulfone 130 (Scheme 45) heated in acetone containing sodium hydroxide rearranged to sulfinic acid derivative 132. After expulsion of SO2,3-acetamido-4-phenylfurazan 133 was formed in 86% yield. Amido-sulfide 131 under similar conditions underwent hydrolysis only to afford the respective acid. 

Addition of oxygen and nitrogen nucleophiles to the dioxide 128 yielding 129 and 130, respectively, is reversible [199], while amine adducts of the dioxide 131 undergo ring opening to give sulfinic acid derivatives 132 (Scheme 72) [200]. 

Sulfinyl chlorides, analogously to sulfonyl chlorides, are important starting materials for the preparation of other sulfinic acid derivatives. Thus, when warmed with alcohols they give sulfinic esters,712 713 and esterification can also be carried out by the Schotten-Baumann procedure in the presence of pyridine or potassium carbonate.714... 

Numerous heterocyclic compounds can be oxidized with ozone to deliver derivatives useful in synthesis and the reaction products can be tuned according to the additives and conditions in the reaction medium. When treated with ozone, pyrimidine-2-thiones and 2-thiouracils react to give several p3Timidine derivatives (eq 57). Use of aprotic solvents or ozonolysis without an active nucleophile yields dimerization products, whereas ozonolysis in protic solvents or in the presence of a nucleophile leads to the sulfinic acid derivative that can then be converted to several products depending on workup conditions. The parent pyrimidine can be isolated when acid is introduced into the medium, and with an equal volume of water the pyrimidinone product is isolated. While a protic solvent, EtOH in the medium acts as a nucleophile to deliver the 2-ethoxypyrimidine. 

A number of enantiopure sulfinic acid derivatives, including sultines 54 and 55, sulfinainides 56-59, sulfinimines 60 and 61, and the chiral sulfoxide 62, were synthesized from (15)-camphorsulfinic acid that was formed by reduction of (15)-camphorsulfonyl chloride with sodium borohydride. ... 

The synthesis of retinoids by sulfonylalkylation has the advantage that the auxiliary substance in the (C15 + C5) linking, i.e., the sulfinic acid derivative, is obtained in the elimination step in a form such that it can be directly used for a further synthesis cycle. In contrast, the triphenylphosphine oxide formed in Wittig reactions first has to be reduced again to triphenylphosphine. However, the range of application of the sulfinate method in retinoid chemistry is still to be established, as has been done for the Wittig reaction in the past 30 years. 

The reaction of peroxyesters, hydroperoxides or peroxides, which are more storage stable than BP, with tertiary amines is generally too slow to give a sufficiently rapid cure for acrylic resins. Composite mixes containing t-butyl perbenzoate, -butyl hydroperoxides or dicumyl peroxide-tertiary amines do not harden for days. Many other redox systems have been suggested for vinyl polymerizations, only a few have been employed in dental resins. Substitution of 2 toluene sulfinic acid or sulfinic acid derivatives for tertiary amines yields colorless products (38-42). Most of these compounds have poor shelf-life. They readily oxidize in air to sulfonic acids which do not activate polymerization. Lauroyl peroxide in conjunction with a metal mercaptide (such as the zinc hexadecyl mercaptide) and... 

Similar halogenations have been done on 2-lithio-l-phenylsulfonylindole[2], 2-Lithio-l-phenylsulfonylindole is readily converted to the 2-(trimethylsilyl) derivative[2,3]. 2-Trialkylstannylindoles can also be prepared via 2-lithio-indoles[4,5], 2-Sulfonamido groups can be introduced by reaction of a 2-lithioindole with sulfur dioxide, followed by conversion of the sulfinic acid group to the sulfonyl chloride with A-chlorosuccinimide[6]. 

Thiourea dioxide, or formamidine sulfinic acid, is an oxygenated thiourea derivative synthesized by the oxidation of thiourea with hydrogen peroxide. It has the chemical formula (NH2)NHCS02H and is tautomeric. 

Carbon-sulfur bonds can be formed by the reaction of elemental sulfur with a lithio derivative, as illustrated by the preparation of thiophene-2-thiol (201) (700S(50)104). If dialkyl or diaryl disulfides are used as reagents to introduce sulfur, then alkyl or aryl sulfides are formed sulfinic acids are available by reaction of lithium derivatives with sulfur dioxide. 

Sulfinyl chlorides may be prepared from the corresponding thiols or disulfides by oxidative reactions rather than by reductions of sulfonyl compounds. A recent example, which improves the earlier procedure of Douglass, is given by equation (3)50. The chemistry of sulfinic acids and their derivatives has been reviewed51 52,53. 

This reaction type has been intensely studied °. The application of highly polar solvents, catalysis with tertiary amines" or with acids mesomeric stabilization of intermediate carbenium ions " (allylic and benzylic systems propargylic systems" ) as well as derivatives of sulfinic acids with increasing acidity - usually indicate an ionic pathway (intra- and/or inter-molecular) ... 

The l3C chemical shifts of methyl derivatives with sulfur substituents [e.g., SH, -S, -SCH3, -SSCH3, -SSSCHj, -S(0)CH3, -S02CH3, -S(CH3)2+, -SC(0)CH3, -SC(S)CH3, and -SC(S)SCH3] (130,131) and of vicinal and gem-inal bis-sulfides (290) have been reported. Freeman and co-workers have published similar studies on thiols, sulfides, disulfides, and sulfinic and sulfonic acid derivatives (131,132,433) and Tseng and Bowler (434), on thiocarbamates, their S-oxides and S,5-dioxides [R-X-C(0)-NR 2 with X = S, SO, S02]. 

An important drug in the present context is the mineralocorticoid receptor antagonist spironolactone (7.74, Fig. 7.12). Among its many metabolic reactions, spironolactone is readily hydrolyzed at the thioester bond (Fig. 7.12, Reaction a) to form deacetyl-spironolactone (7.75, Fig. 7.12), a metabolite found in a variety of tissues [155 -157]. This thiol compound, which is also a potent mineralocorticoid antagonist, promotes the mechanism-based inactivation of hepatic, adrenal, and testicular cytochrome P450 isozymes. There is now good evidence to indicate that this behavior is the result of microsomal 5-oxidation (see Chapt. 7 in [7]). When spironolactone was incubated with liver microsomes from rats pretreated with dexamethasone (an inducer of CYP3A), the sulfinic and sulfonic acid derivatives were characterized [158]. Perhaps the importance of the 5-deacetylation of spironolactone... 

The ORD and CD curves of chiral sulfinamides derived from aromatic sulfinic acids show a strong Cotton effect centered at 240 to 256 nm (83). The position of this Cotton effect, its dependence on the solvent used, and the amplitude reveal a complete analogy with that observed in alkyl aryl sulfoxides and aromatic menthyl sulfin-ates. Thus, the positive sign of the Cotton effect observed in the ORD curves of dextrorotatory sulfinamides is indicative of the (5)-configuration around sulfur in these compounds. 

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