Thioalkyl derivatives

The interaction of alkyl halides with mercaptans or alkaline mercaptides prodnces thioalkyl derivatives. This is a typical nncleophilic substitution reaction, and one cannot tell by the nature of products whether or not it proceeds through the ion-radical stage. However, the version of the reaction between 5-bromo-5-nitro-l,3-dioxan and sodium ethylmercaptide can be explained only by the intermediate stage involving electron transfer. As found (Zorin et al. 1983), this reaction in DMSO leads to diethyldisulfide (yield 95%), sodium bromide (quantitative yield), and 5,5 -bis(5-nitro-l,3-dioxanyl) (yield 90%). UV irradiation markedly accelerates this reaction, whereas benzene nitro derivatives decelerate it. The result obtained shows that the process begins with the formation of ethylthiyl radicals and anion-radical of the substrate. Ethylthiyl radicals dimerize (diethyldisulfide is obtained), and anion-radicals of the substrate decompose monomolecularly to give 5-nitro-l,3-dioxa-5-cyclohexyl radicals. The latter radicals recombine and form the final dioxanyl (Scheme 4.4). 

Treatment of 13 with dimethyl sulfate,or other alkyl halides, - and base leads to the thioalkyl derivatives 16 in high yields (Scheme 7). The 0X0 analog of 12 (R = Ph) is methylated at the ring nitrogen atom. ... 

Esterases of the Juvenile Hormone of Insects Many works have been dedicated to the inhibition of esterases of the juvenile hormone of insects. The purpose of these works is to control insect populations by ehminating their metamorphosis. Among the numerous trifluoromethyl ketones that have been synthesized, thioalkyl derivatives of trifluoroacetone have been shown to be the most active ones. Curiously, the corresponding alcohols are also excellent inhibitors. Trifluoromethyl ketones can also inhibit other insect esterases antenna esterases and esterases that are involved in the release of pheromones (Figure 7.33). The inhibition of these latter ones can also be interesting for insect control purposes. 

The thioalkyl-containing macrobicyclic complexes have been dealkylated and realkylated easily under the action of potassium thiolates in aprotonic media (Scheme 14). The products of de- and realkylation reactions were detected by PD and FAB mass spectrometry. In this respect the thioalkyl-containing clathrochelates are close to the aryl alkyl sulfides. In the course of thioalkyl derivative synthesis with an excess of potassium thiolate, a mixture of dealkylated products was obtained in addition to the desired hexathioalkyl clathrochelates. The addition of corresponding alkyl iodide and potassium carbonate to the reaction mixture in the final stage of reaction led to an increase in yields by alkylation of HS groups, resulting in the side dealkylation process [65]. 

For the simple silyl perchlorates Me3SiC104 and Ph3SiC104 the Si chemical shifts are about 47 and 3 ppm, respectively, the values depending a little on the solvent used . Reliable chemical shifts for ( -PrS)3SiC104 and other thioalkyl derivatives have not been obtained because of the poor stability of these ions in solution. The chemical shift of Me3SiC104 varies little for either neat liquid or sulpholane solutions at concentrations of 0.584, 0.29 and 0.15 moldm, clearly indicating covalency over this range of concentrations. This seems to contradict the results of the C1 NMR study described above which indicated that at these three concentrations there were 20 5, 29 5 and... 

Other nucleophiles, including mercaptans, carbanions, and enamines (Fig. 18) (60), can also add in a conjugate fashion to the quinone ring but the derivatives obtained have not proved to be useful as antibacterial agents. The thioalkyl derivatives (40) were quite active in vitro but were not orally absorbed, while the carbanion addition products (41) were good inhibitors of bacterial DNA-directed RNA polymerase but were relatively inactive on bacteria. The enamine products (derived by cyclization of 42) were quite complex and their activity does not appear to have been reported. 

Z-Bromodithioketene acetal derivatives (15) can be transformed into 2-thioalkyl-substituted penems (16) by copper(I) halides39 (Scheme 18). The process is especially attractive because of the ready availability of requisite functionalized secolactams (cf. 15) and also because of the tolerance of a variety of functional groups to the cyclizing agent. 

This procedure demonstrates a particularly effective method for controlling the relative and absolute stereochemistry of the aldol reaction. It is quite general in scope. Alkyl-, aryl, and a,6-unsaturated aldehydes all give good results. In addition to chiral propionates, a range of related aldol reactions may be carried out. For example, the analogous aldol reactions of thioalkyl, benzyloxy, or haloacetate, as well as succinate- and crotonate-derived carboximides, have been reported. 

Numerous researchers have employed thiols as weak bases in the thioalkylation reaction to ligate unprotected peptides with a haloacetyl group to form thioethers at pH 7 8.5[90 91 131-133 or thioesters at acidic to basic conditions. 108"110 Of these two reactions, thioether formation is often the choice because thioesters suffer from instability in aqueous basic conditions. Haloacetyl derivatives, either as carboxylic acids or active esters, can be attached to either the N-terminal or side-chain amines during the stepwise solid-phase synthesis of either the peptide or the core and are stable to either HF or TFA cleavage conditions. Capping an amino group with a chloroacetyl group is compatible with Fmoc chemistry when used at a terminal step. 

Pyrimidine derivatives, (n), prepared by Bethiel (3) and thioalkyl 1,3, pyrimidine derivatives, (HI), prepared by Choon-Moon (4) were effective as c-JNK inhibitors and kinases belonging to the Src family of protein kinases. 

Strained -oxidoalkyl i enyl selenoxides, such as l-oxido-l-(r-phenylsdenoxyalkyl)cyclopropanes, derived from oxaspiropentanes with tetraalkyl-substituted oxirane rings, and l-(r-hydroxyalkyl)-l-selenoxycyclobutanes, - obtained on oxidation of the corresponding selenides or on reaction of a-li-thioalkyl selenoxides with cyclobutenones, possess a high propensity to rearrange to cyclobutanones... 

Sulfur- and Selenium-containing Compounds. A new route to a-thioalkyl-phosphonates (292) and -phosphinates (294) has been reported from the reaction of selenothioic acid S-esters (291) with phosphites and phosphinites, respectively. By-products (293), derived from the P(III) ester alkylating the Se atom, are formed in many cases. a-Phosphono-p-substituted a,P-unsaturated dithioesters (296), prepared from diethyl phosphonodithioacetate (295), undergo Diels-Alder reactions with enol and thioenol ethers to give excellent yields of novel 5-... 

Acid hydrolysis will often convert thione, thioalkyl, and imino derivatives into the oxy analogues, and sulfur functions can also be directly oxidized to oxo <85PS(22)49, 91TL4791>. When mercuric acetate was used to convert the l,3-diacylimidazolidin-2-thione (138) into the corresponding imi-dazolidinone (139) the process was believed to proceed as in Scheme 70. 

The reactivity of B-substituents in 2,3-dihydro-1,3-diboroles can be studied by means of a few examples. 1,3-Diodo-l,3-diboroles can be transformed into the alkoxy, thioalkyl, and chloro derivatives (Scheme 5) <85ZN(B)326>. 

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