Thiomethyl

In a similar way, the a-haloketones gives the corresponding 2-thiomethyl-3-ethylthia2olium salts (722). 

A somewhat more circuitous route is required to prepare sulfonamide-containing pyrimidines unsubstituted at 2. Thus, acylation of the 2-thiomethyl pyrimidine, 147, with the sulfonyl chloride, 88, affords 148. Removal of sulfur by means of Raney nickel (149) followed by deacetylation gives sulformethoxine (113). ... 

The 5-methoxy seems less critical its replacement by methylthio or ethylthio groups, especially in 3,4,5-substituted compounds, has recently been explored by Jacob and Shulgin (116). Activity in this series is not reduced. Recently, the authors (117) prepared the 2- and 5-thio isosteres of DOM and DOET. With a 2-thiomethyl, activity was retained but was attenuated to about 1/20 to 1/25 of the oxygen isosteres. The 5-thiomethyl isomers possessed two to four times the activity of the thiomethyls at the 2-position. When both the 2- and 5-methoxys were replaced by thiomethyl groups, activity was essentially abolished. 

In order to synthesize biologically relevant phosphonylimidazole 73, bromoimidazole 72 was derived from radical-initiated bromination of methyl l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (71) [56]. The thiomethyl group served to block the C(2) position, which would otherwise undergo preferential halogenation under these conditions. As expected, a variety of Arbusov-Michaelis reaction conditions failed even under forcing conditions. On the other hand, Pd-catalyzed phosphorylation of 72 with diethyl phosphite led to methyl-4-diethylphosphonyl-l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (73). After further manipulations, the desired phosphonic acid-linked aminoimidazoles, which resembled intermediates formed during purine biosynthesis, were accessed. 

A quite simple way to form the oxazolo[3,4- ]pyridine or thiazolo[3,4- ]pyridine ring system is to build the five-membered ring, respectively, starting from a 2-hydroxymethyl-piperidine or 2-thiomethyl-piperidine. The reaction of the latter compounds with aldehydes, acetals, phosgene, carbonates, or synthetic equivalents have been known for years and will therefore not be detailed here. Representative and typical examples are summarized in Table 10. 

Table 10 Formation of saturated oxazolo[3,4-a]pyridines or thiazolo[3,4-a]pyridines from 2-hydroxymethyl-piperidines or 2-thiomethyl-piperidines...

Tumelty, D. Schwarz, M. K. Needels, M. C. Solid-Phase Synthesis of Substituted l-Phenyl-2-aminomethyl-benzimidazoles and l-Phenyl-2-thiomethyl-benzimidazoles, Tetrahedron Lett. 1998, 39,1461. 

Whereas the radical anion formed from l-methyl-2(thiomethyl)imidazole has a 7r SOMO, 4-bromo- and 4-iodo-2-methylimidazole, 5-bromo- and 5-iodo-l,2-dimethylimi-dazole and 4,5-dibromo- and 4,5-di-iodo-l,2-dimethylimidazole form cr radical anions in irradiated methanol or MeTHF solutions at 77 K251. 

The 5-thione analogue of Step 3, l-(3-pyridinylamine-2-thiomethyl-4-methyl-4-phenyl-2-imidazolin-5-thione, (II), and derivatives were previously prepared by the author and are described (1). 

The synthesis and biological activity of 2,4,6-triamino-substituted-1,3,5-tiiazines have been described <03JIC138>. The synthesis of //-substituted 2,4-diamino-6-(benzothiazolyl-2-thiomethyl)-l,3,5-triazines 11 has been achieved from guanidine derivative 9 through intermediate 10 <03KGS730>. 

Scheme 20. Proposed reaction sequence for electrochemical reduction of 4,6-dimethyl-2-thiomethyl-pyrimidine at the DME...

In their earlier work, Michel, Epp, and Deisenhofer crystallized Rp. viridis reaction center with the vacant Qg site reconstituted with either o-phenanthroline (OP) or terbutryn (2-thiomethyl-4-ethylamino-6-t-butylamino-5 -triazine and abbreviated as TERB ) and were able to identify three binding locations for OP and one for TERB. In Eig. 10 (B), OP is shown seated deep within the pocket. Each of the two N-atoms (shaded) of OP form a hydrogen bond with the imidazole nitrogen of His 190. In addition, OP is also close to Ile229 and Leu 193 (neither shown in the figure). 

TERB - terbutryn (2-thiomethyl-4-ethylamino-6-f-butylamino- -triazine)... 

When a 2-thiomethyl-l,3-selenothiolium iodide such as (84) reacts with an aryl ketone (85) in pyridine-acetic acid, fulvenes such as (86) are obtained reaction with a Wittig-Homer reagent takes place at both carbonyl groups (Equation (8)) <90PAC473,91JCS(Pl)157>. 

The second stage is a reaction S-sodium compound of 2-thiouracil with methyl(benzyl)bromid and obtaining of 2-thiomethyl(benzyl)-4-pyrimidinon. Reaction of nucleophilic substitutiof bromine in methyl (benzyl) bromid by anion, generated from 2-thiouracil is shown on scheme... 

Reaction with 1,3-dithianes. The special reactivity of 2-thiomethyl-l,3-dithianes has been exploited. The thio group is eliminated to provide 2-methylene-1,3-dithiane which is susceptible to attack by organohthium reagents. Trapping of the dimeric dithianyllithium species leads to precursors of various 1,3-diketones. 

Thioridazine (No. 5) undergoes an additional sulfoxidation at the 2-thiomethyl group. However, in this case the metabolite produced is active and marketed as mesoridazine (No. 4). 

Figure 14 Chemical structures of m G, yW, i A, ms A, and Q. i A and t A are found both with and without the 2-thiomethyl group that can further increase base stacking with a nucleotide in the first codon position (cross-strand stacking).

In 1968 Verkade and co-workers described what is to our knowledge the only 2,6,7-trithia-l-arsabicyclo[2.2.2]octane (257), by reaction of 2-(thiomethyl)-2-methyl-l,3-propanedithiol (256) with AsClj (Equation (43)) <68IC1469>. 

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