Thiols, -alkoxy

Sulfides are the sulfur analogs of ethers just as thiols are the sulfur analogs of alcohols. Sulfides are named by following the same rules used for ethers, with sulfide used in place of ether for simple compounds and alkylthio used in place of alkoxy for more complex substances. 

Some limitations of the method arise due to side reactions involving the nitroxide. However, such problems can usually be avoided by the correct choice of nitroxide and reaction conditions. Nitroxides, while stable in the presence of most monomers, may act as oxidants or rcductants under suitable reaction conditions.516 The induced decomposition of certain initiators (e.g. diacyl peroxides) can be a problem (Scheme 3.94).166 177 There is some evidence that nitroxides may disproportionate with alkoxy radicals bearing a-hydrogens,123 Side reactions with thiols have also been identified.4 18... 

Another remarkable reaction is the nucleophilic substitution of the chlorine by alkoxy or sulfido groups using the alcohol or the thiol and the weak base Na2C03 in situ. For example, in the case of ethanol, the reaction proceeds in 12 h at reflux Eq. (23), Table 3. 

The reaction of 3,4-bis(benzenesulfonyl)furoxan with alcohols and thiols in basic media affords a variety of alkoxy-and alkylthio-substituted (benzenesulfonyl)furoxans. For these derivatives a paramount problem is to determine the position (3- or 4-) of the substitution in the furoxan ring. The structures of these derivatives were assigned on the basis of both chemical and NMR evidence. In particular, 13C NMR substituent constants were obtained by NMR study of suitable furoxan models. By assuming a complete additivity of the substituent effects at the furoxan ring, these values were used for structural determination <1997FES405>. 

Miscellaneous. The reaction of the aminophosphonium salt (156) with thiols and alkoxides affords a convenient, high-yield, single-step synthesis of unsymmetrical thioethers.141 The key intermediate is the alkoxyphosphonium salt (157), which undergoes nucleophilic attack by RS- at the alkoxy carbon. 

The chemical diversity of carboxylic acid esters (R-CO-O-R ) originates in both moieties, i.e., the acyl group (R-CO-) and the alkoxy or aryloxy group (-OR7). Thus, the acyl group can be made up of aliphatic or aromatic carboxylic acids, carbamic acids, or carbonic acids, and the -OR7 moiety may be derived from an alcohol, an enol, or a phenol. When a thiol is involved, a thioester R-CO-S-R7 is formed. The model substrates to be discussed in Sect. 7.3 will, thus, be classified according to the chemical nature of the -OR7 (or -SR7) moiety, i.e., the alcohol, phenol, or thiol that is the first product to be released during the hydrolase-catalyzed reaction (see Chapt. 3). Diesters represent substrates of special interest and will be presented separately. 

Structures of this type were generated in the reaction of Af-acyloxy-Af-alkoxyamides with thiols. Treatment of Ai-acetoxy-iV-butoxybenzamide (145, R = Bu, = Me) and a series of Ai-benzoyloxy-Ai-benzyloxybenzamides (139) with cysteine derivatives generated disulfides and hydroxamic esters (Section IV.C.3.b, Scheme 24). The intermediate Ai-alkoxy-Ai-thioalkylamides were unstable under the reaction conditions, reacting with a second thiol molecule at sulfur. The reaction of thiols at the anomeric nitrogen of Af-acyloxy-Ai-alkoxyamides has been modelled theoretically and is predicted to be favourable energetically, leading to a stable substitution product ... 

The presence of nitro, carboalkoxy, carboxyl, chloro, formyl, alkyl, and acyl groups does not interfere with the reaction. A single alkoxy group also does not interfere, but if two or more are present, the yields are markedly decreased. The reaction is inhibited by the presence of unhindered, basic nitrogen substituents, by the phenolic group, and probably by the thiol group. 

Besides alkoxy-, amino-, and amidocarbonylation reactions, a carbonylation process using a thiol as nucleophile, that is, thiocarbonylation, has been extensively studied.It has been shown that the thiocarbonylation takes place with 1-alkynes, " " " propargyl alcohols,allenes, " 1,3-dienes, propargylic mesylates, " and bicyclopropylidene . 

It is somewhat surprising that in l.l-bis-dialkylamino-2.4.6-triphenyl-X -phosphorin both dialkylamino groups are replaced by SR groups in the presence of thiols, whereas the 1-alkoxy-1-dialkylamino-X -phosphorin fails to react at all under the same reaction conditions. 

Halogen atoms in cationic olium rings are very reactive. The halogen atom in the quaternary salts of 3- and 5-halo-1-phenylpyrazoles is replaced at 80-100°C by hydroxy, alkoxy, thiol, amino or cyano groups (66AHC(6)347). 3-Halo-1,2-dithiolyliums are converted into l,2-dithiol-3-ones by water and react readily with other nucleophiles (80AHC(27)l5i). 

Usually, 3- and 4-substituted thianes are prepared from the 3- and 4-oxothians by the common techniques applicable to alicyclic chemistry. Reduction affords alcohols which may be etherified or halogenated, while oximation and reduction produces the amino derivatives, which are also accessible via the halo compounds. 2-Alkoxy and 2-alkylthio compounds are made by acid catalyzed addition of alcohols and thiols to 3,4-dihydro-2H-thiopyran (75MI22502) in a reaction analogous to the use of dihydropyran for protection of alcohols as THP ethers. 

Isothioureas can be prepared on insoluble supports by S-alkylation or S-arylation of thioureas (Entry 7, Table 14.6). Further methods for the preparation of isothioureas on insoluble supports include the N-alkylation of polystyrene-bound, A/,/V -di(alkoxy-carbonyl)isothioureas with aliphatic alcohols by Mitsunobu reaction (Entry 7, Table 14.6) and the addition of thiols to resin-bound carbodiimides [7]. Resin-bound dithio-carbamates, which can easily be prepared from Merrifield resin, carbon disulfide, and amines [76], react with phosgene to yield chlorothioformamidines, which can be converted into isothioureas by treatment with amines (Entry 8, Table 14.6). The conversion of support-bound a-amino acids into thioureas can be accompanied by the release of thiohydantoins into solution (see Section 15.9). The rate of this cyclization depends, however, on the type of linker used and on the nucleophilicity of the intermediate thiourea. 

This route has many ramifications depending on the nature of R and R" in Scheme 2 thus R may be alkyl, aryl, amino (thioamide), alkylthio, or thiol and R" may be alkyl, aryl, amino (amidine), hydroxy (amide), or alkoxy (imino ether), although as yet not all of the possible combinations of these groups has been fully examined. In practice, the utility of the route depends on the availability of the requisite intermediates, and the situation is further complicated by the numerous routes which have been devised to these precursors. 

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