Alkylthio Substituents

2-Methylthiopyrazine reacts with methoxide ion at elevated temperatures to give 2-methoxypyrazine, and the kinetics have been determined (Section 3) (1080). Anhydro-2,6-dihydroxy-l,4-diphenyl-3,5-bis(phenylthio)pyrazinium dihydroxide, for example, (14), with a saturated solution of hydrogen chloride in acetic acid at room temperature gave 2,3-dioxo-l,4-diphenyl-5-phenylthio-l,2,3,4-tetrahydro-pyrazine (6.4%) (15) and l,4-diphenyl-6-phenylthiopiperazine-2,3,5-trione (60%) (476a). 

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With a carboxy group on the alkyl chain of the alkylthio substituent. C-4 may be involved in an intramolecular nucleophilic substitution to give 159 (Scheme 84). 

Sometimes lateral chlorination can occur on a methyl or alkylthio substituent, especially when phosphorus pentachloride or its mixtures with phosphoryl chloride are used (91JHC1549). Reactions of 2-methyl-4(I//)-quinoline (67) exemplify this behavior (81CPB1069) (Scheme 31) 2-chloro-3- and -4-methyquinolines are also subject to methyl chlorinations by similar reagents (91JHC1549). Sulfuryl chloride and NCS are also likely to induce a proportion of lateral chlorination (83KFZ1055 86S835). 

An alkylthio substituent at the 4-position increases activity and also brings... 

Neighboring group participation effects appear to play a crucial role in the nucleophilic substitution of chlorine in Michael adducts of 1-R, 2-R, 3-X. Thus, this substitution proceeds very easily in any of the adducts formed with an electron rich nitrogen, sulfur and oxygen Michael donor. For the adducts of nitrogen nucleophiles, the facile substitution of the chlorine has been suggested to occur via formation of intermediate aziridinium ions 103 [8] (Scheme 32), and this postulate was later supported by isolation of azaspiropentane derivatives under appropriate conditions in several reactions (see Sect. 3.2.2) [11b, 53,56]. It is most likely that alkylthio substituents in adducts of type 85 participate in the same way to first form spirocyclopropane-annelated thiiranium ion intermediates which are subsequently opened by attack of the incoming nucleophile. 

Despite all of the activity in pyrimidine-based synthesis, only one study has emerged of solid-phase versions of these reactions <2003TL1267, 20030BC1909>. This chemistry was based upon condensation of dicarbonyl compounds with resin-bound pyrimidine-5,6-diamines through a 2-alkylthio link and oxidative cleavage as described in Section 10.18.7.2. The value of alkylthio substituents in the synthesis of complex substituted pterins has also been demonstrated in the synthesis of nucleic acid conjugates <2004OBC3588> (see Section 10.18.12.4). 

Alkoxy substituted thiopyrylium compounds are obtained by hydride abstraction from the thiin precursor with trityl salts, or by elimination of halogen from a thiin. By contrast, alkylthio substituents may be generated in creating the cationic species as shown in equation (115), though of course only 2- and 4-substituents are available in this way (76CC899). Amino substituted compounds may be prepared by substitution of the methylthio groups, but the nature of the product is strongly dependent on the nature of the amine (see Section 2.25.3.4). 

The copper(I)-catalyzed addition of Grignard reagents to P-(alkylthio)-a,p-unsaturated esters is the preferred protocol for substitution of the alkylthio substituent, e.g. (310 - 311),21 while potassium enolates add to a-ketoketene dithioacetals, e.g. (312 — 313), without dialkylation (Scheme 96).218b,c Further, Hanessian reports an expedient synthesis of penam (315) via intramolecular cyclization of the (3-lactam nitroalkene (314), but loss of the methylthio moiety does not occur spontaneously (Scheme 97).219... 

A large shift to NIR region was in particular observed for SnPc complexes containing alkylthio substituents, Table 1, Fig. 7. The nonperipherally substituted... 

The detection of many analytes on unmodified electrodes occurs at high potentials, hence the need for modified electrodes. Even though different types of SAMs have been reported, only a few of them have been employed as catalysts for electrochemical reactions. Most work has concentrated on the characterization of SAMs, with limited studies devoted to detection. Table 3 summarizes the analytes which have been detected by employing NIR-absorbing MPcs (such as MnPc and TiPc) containing amino or alkylthio substituents. In Table 3, the electrodes are modified by SAMs, polymers, electrodeposion, and adsorption. 

Cyclocondensations involving thioxo or alkylthio substituents are represented by the conversion of 6-methyl-4-(thien-2-yl)-2-thioxo-l,2,5,6,7,8-hexahydro-l,6-naphthyridine-3-catbonitrile into 4-hydroxy-9-methyl-4-(thien-2-yl)-7,8,9,10-tetrahydropyrido 2, 3 4,5 thieno 2.3-ft [ l,6Jnaphthyridin-2(17/)-one (3) (ClCH2C0CH2C02Et, EtOH, EtONa, reflux, 10 min 88%) 1429 also of 2-acetonylithio-8-benzylidene-6-isopropyl-4-phenyl-5,6,7,8-tetrahydro-l,6-naphthyridine-3-carbonitrile into 2-acetyl-8-benzylidene-6-isopropyl-4-phe-nyl-5,6,7,8-tetrahydrothieno 12,37 1,6]naphthyridin-3-amine (4) (EtONa, EtOH, 20°C 15 min 75%).946... 

Arylthioimidazoles can be made in high yields when thiophenates react with At-(l-cyanoalkyl) alkylidene A -oxides. Alkyl and aralkyl thiolates, however, react much less readily (see Section 2.1.1 and Scheme 2.1.10). Imidazole-4-thioethers can be made in a general reaction between nitriles and a range of isocyanides which are susceptible to o -metallation (see Section 4.2, Scheme 4.2.2 and Table 4.2.1). Oxoketene acetals bearing alkylthio substituents react with nitrosoaromatics to give 5-acyl-4-alkylthio-l-arylimidazoles in moderate to good yields (see Section 3.2 and Scheme 3.2.5). 

TABLE XXI. 3-Pyrazolin-5-ones. Alkoxy, Aryloxy, Acyloxy, and Alkylthio Substituents... 

Thiols are also useful sources of the corresponding bromo compounds, by reaction with bromine and hydrobromic acid." Alkylthio substituents can be displaced by the usual range of nucleophiles, but the corresponding sulfones are more reactive. " ... 

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