Diethylamino sulfur synthesis

Compounds bearing C(=S)-NH-C-C-OH fragment ((3-hydroxy thioamide) can also undergo cyclodehydration to form thiazoline derivatives. The utility of this strategy has been demonstrated in the synthesis of halipeptins A and D <06JA4460>. Exposure of 73a/b with (diethylamino)sulfur trifluoride (DAST) brings about intramolecular cyclization to provide thiazolines 74a/b, which are advanced precursors to halipeptins A and D. 

As described previously, thiazohnes are versatile intermediates to thiazoles. In addition, thiazoline rings are structural motifs found in numerous natural products. Among a variety of methods for the construction of thiazolines, the cyclodehydration protocol is perhaps most popular. In the total synthesis of cyclopeptide YM-216391, (diethylamino)sulfur trifluoride (DAST) is used as the cyclodehydrating agent for the conversion of P-hydroxy thioamide 76 to thiazoline 13 <05CC797>. A similar strategy has been used in the construction of the thiazoline moiety in two independent total syntheses of hahpeptin A (77 to 78 79 to 80)... 

J.R. McCarthy, NP. Peet, ME, LeToumeau, and M. Inbasekaran, (Diethylamino)sulfur trifluoride in organic synthesis. 2. The transformation of sulfoxides to a-fluoro thioethers, J, Am, Chem, Soc, 107 735 (1985). 

MJ. Robins, K.B. Mullah, S.F. Wnuk, and N.K. Dailey, Nucleic acid related compounds. 73. Fluorination of uridine 2 -thiocthers with xenon difluoride or (diethylamino)sulfur trifluoride. Synthesis of stable 2 -[alkyl(or aryl)sulfonyl]-2 -deoxy-2 -fluorouridines,/. Org, Chem, 57 2357 (1992). 

Symmetrical sulfides are obtained in 70-90% yields by refluxing aqueous alcoholic solutions of halides with sodium sulfide. The nonahydrate of sodiiun sulfide is a satisfactory reagent for the reac-tion. Tetramethylene and pentamethylene halides give cyclic sulfides, e.g., tetramethylene sulfide (tetrahydrothiophene) (64%). Halides containing several other important functional groups have been employed. Typical examples include methallyl chloride, and halides with hydroxyl, ethoxyl, carboxyl, and diethylamino groups in the beta position. A dry synthesis of phenyl sulfide from calcium oxide, sulfur, and chlorobenzene at 300° has been reported. ... 

Dichlorobenzaldehyde is activated for the phase transfer step as the cyano-diethylamino-adduct. 3-Chloromethylpyridine is prepared from 3-hydroxymethyl pyridine by treatment with thionylchloride. The hydrochloride salt of the product is taken up in water and the solution is tised directly in the phase transfer step. Strict temperature control, proper speed of addition of the 3-chlormethyl -pyridine solution and the use of a cosolvent like e.g. hexane ensure a reliable yield of enamine greater than 95%. The enamine reacts at room temperature quantitatively with the hydrochloride salt of 0-methylhydroxylamine to give the corresponding oxime ether as an E/Z-mixture of 3 7. Addition of sulfuric acid to this oximation reaction and an increase of reaction temperature to about 50 C yields pyrifenox rapidly in the desired E/Z-equilibrium ratio of about 1 1. No special purification processes are required in the whole synthesis. 

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