Syntheses, 2-alkylthio derivatives

Amino-5-alkyl- or 5-phenyI-l,3,4-thiadiazoles are prepared most conveniently from thiosemicarbazide. For example, benzalthiosemicarbazone by oxidation with iron(III) chloride gives the 5-phenyl derivative. Thiosemicarbazide is also used in the synthesis of 2-amino-5-mercapto-l,3,4-thiadiazole by reaction with carbon disulfide. The product may be alkylated to yield the 5-alkylthio derivatives using a variety of alkylating agents (58MI11201). 

The thioboration of terminal alkynes with 9-(alkylthio)-9-borabicyclo[3.3.1]-nonanes (9-RS-9-BBN) proceeds regio- and stereoselectively by catalysis of Pd(Ph,P)4 to produce the 9-[(Z)-2-(alkylthio)-l-alkeny)]-9-BBN derivative 667 in high yields. The protonation of the product 667 with MeOH affords the Markownikov adduct 668 of thiol to 1-alkyne. One-pot synthesis of alkenyl sulfide derivatives 669 via the Pd-catalyzed thioboration-cross-coupling sequence is also possible. Another preparative method for alkenyl sulfides is the Pd-catalyzed cross-coupling of 9-alkyl-9-BBN with l-bromo-l-phe-nylthioethene or 2-bromo-l-phenylthio-l-alkene[534]. 

A novel synthesis of alkylsulfanylisothiazoles 230 starts with sodium a-cyanoketene dithiolates 227, obtained by the reaction of cyanoacetamides 226 with carbon disulfide in the presence of sodium ethoxide <06SC825>. Treatment of 227 with sulphur and piperidine acetate generates sodium isothiazole-3,5-dithiolates 229. The formation of 229 is assumed to arise from the addition of anionic sulphur to the nitrile group in 227 to give the intermediate 228, which cyclizes upon elimination of anionic sulphur to yield 229. Salts 229 are readily alkylated to furnish 3,5-bis(alkylthio)isothiazole derivatives 230. 

The synthesis and the antifungal, anti-inflammatory and analgesic effects <2006MI4>, or antimicrobial activity <2006MI5> of novel l-alkyl-2-alkylthio-l,2,4-triazolobenzimidazole derivatives have been communicated. 

The protonation of 185 and 186 with trifluoroacetic acid (TFA) gave 4-(/i t/-butylthio)-3,6-diphenyl- 193 and 4-(ter1-butylthio)-3,6-di(2-thienyl)thieno[3,4-f]thiophene-l(3//)-thione 194 (Scheme 18). The treatment of 193 with sodium hydride and then isopropyl iodide led to 4-(/i< t/-butylthio)-3,6-diphenyl-l-(isopropylthio)thieno[3,4-f]thio-phene 195 by the regeneration of the thieno[3,4-f]thiophene ring system, thus making possible the synthesis of other alkylthio-substituted thieno[3,4-(r]thiophene derivatives. When the reaction of 185 with TFA was carried out... 

G. S. Bethell and R. J. Ferrier, The relayed introduction of alkylthio-groups into carbohydrates derivatives A novel synthesis of amicetose, J. Chem. Soc. Perkin / (1993) 1400-1405. 

The addition of sulfur radicals to isocyanides produces imidoyl radicals as intermediates. The stereocontrolled 5-exo-trig cyclization of imidoyl radicals in the synthesis of substituted (alkylthio)pyrrolines, pyroglutamates, and thiopyroglutamates has been reported [95JOC6242], The intermediate 137 is not isolated but undergoes further thermal reaction to furnish a pyroglutamate derivative. 

Agbalyan et al 9 recently employed this reaction in the synthesis of several 3,4-dihydroisoquinoline derivatives with unsaturated substituents in the 1-position. The Madrid group50 has shown that (with the exception of benzyl thiocyanate) aliphatic and aromatic thiocyanates yield 1-alkylthio- and l-arvlthio-3,4-dihydroisoquinolines as expected (cf. Table V). 

Less frequently, unsaturated 1,4-ketoacids were employed and these 207-209 qj. hydrazones afford 12 directly. Synthesis of 12 is also possible from unsaturated y-lactones 210-21S S-bromo-, " 3-alkylthio-, or 2-hydroxy-l,4-ketoacids. The reaction takes place with simultaneous elimination of water or other residues, although it is claimed that in some cases the elimination of water is slower since the corresponding 4-hydroxy derivatives (13) were isolated.However, the structure of the latter compounds... 

Artemisinin has been converted in two steps into the stable trioxane isobutene dimer 41. Reactions at the linking unit leave the trioxane fragments intact and allow the synthesis of a variety of dimers that possess desirable pharmacological properties <03JMC1060>. 10-Bromoalkyl and 10-aminoalkyl derivatives of deoxoartemisinin have been prepared and used to form dimers and a trimer in which artemisinin residues are linked through alkylamide and alkylthio functions <03JMC987>. 

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