Thiazolium, 3-benzyl-5- -4-methyl-, chloride

In the late 1990s, Tins and co-workers described a formal total synthesis of roseophihn [99, 100], The Stetter reaction was well suited for the coupling of partners 157 and 158 in the presence of 3-benzyl-5-(hydroxyethyl)-4-methyl thiazolium chloride (Scheme 24). 

Thiazolium chloride, 3-benzyl-5-(2-hydroxyethyl)-4-methyl-catalyst... 

DIKETONES l-Benzyl-4-(2-hydioxy-ethyl)-5-methyl-l, 3-thiazolium chloride. Copper(II) trifluoromethanesulfonate. 

The thiazolium salt 3-benzyl-5-(2-hydroxyethyl)-4-methyl-l,3-thiazolium chloride is an excellent catalyst for the addition of unsaturated aliphatic aldehydes to vinylketones (79CB84). The presence of a base such as sodium acetate or triethylamine is required, for the thiazolium salt must first be transformed into the ylide structure (615), which then exerts a catalytic effect resembling that of cyanide ion in the benzoin condensation (Scheme 137). Yields of 1,4-diketones (616) produced in this process were generally good. The use of thiazolium salts for other related reactions has been reviewed (76AG(E)639). 

Benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium chloride (4568-71-2), 65, 26 N-Benzylidenebenzenesulfonamide (13909-34-7), 66, 203, 204, 206, 210 Benzylidenemalononitrile Malononitrile, benzylidene- Propanedinitrile, (phenylmethylene)- (2700-22-3), 65, 32 Benzyl mercaptan a-Toluenethiol Benzenemethanethiol (100-53-8), 65, 215 N-BENZYL-N-METHOXYMETHYL-N-(TRIMETHYLSlLYL)METHYLAMINE BENZENEMETHANAMINE, N-(METHOXYMETHYL)-N-[(TRlMETHYL-SILYL)METHYL]- (93102-05-7), 67, 133 1-BENZYLOXY-4-PENTEN-2-OL 4-PENTEN-2-OL. 1 -(PHENYLMETHOXY)- (58931-16-11), 69, 80... 

A. Z, s-Vndeoanediona. A 1000-mL, three-necked, round-bottomed flask equipped with a mechanical stirrer, short gas inlet tube, and an efficient reflux condenser fitted with a potassium hydroxide drying tube is charged with 26.8 g (0.1 mol) of 3-benzyl-5-(2-hydroxyethyl)-4-methyl-l,3-thiazolium chloride (Note 1), 500 mL of absolute ethanol, 77.2 g (1.1 mol) of 3-buten-2-one (Note 2), 60.6 g (0.6 mol) of triethylamlne (Note 3), and 114.2 g (1.0 mol) of heptanal (Note 4). A slow stream of nitrogen (Note 5) is started and the mixture is stirred and heated in an oil bath at 80°C. After 16 hr the reaction mixture is cooled to room temperature and concentrated by rotary evaporation. Then 500 mL of chloroform is added to the residue and the... 

Benzyl-5-(2-hydroxyethyl)-4-methyl-l, 3-thiazolium chloride is supplied by Fluka AG, Buchs, Switzerland and by Tridom Chemical, Inc., Hauppague, New York. The thiazolium salt may also be prepared as described in Org. Synth. 1984, 42, 170. 

Benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium chloride Thiazolium, 3-benzyl-5-(2-hydroxyethyl)-4-methyl-, chloride (8) Thiazolium,... 

Interestingly, the mild reaction conditions of the CIR are fully compatible with the Stetter reaction. As a result a sequence of transition metal, base and organoca-talysis can be easily conceived. Upon CIR of electron-deficient (hetero)aryl halides 11 and (hetero)aryl propargyl alcohols 12, and after subsequent addition of aliphatic or aromatic aldehydes 92 and catalytic amounts of thiazolium salt 93 1,4-diketones 94 are obtained in moderate to excellent yields in a one-pot procedure (Scheme 50) [259, 260]. For aromatic aldehydes the catalyst precursor of choice is 3,4-dimethyl-5-(2-hydroxyethyl) thiazolium iodide (93a) (R = Me), and for aliphatic aldehydes 3-benzyl-4-methyl-5-(2-hydroxyethyl)-thiazolium chloride (93b) (R = CH2Ph) is applied. 

CYCLOHEXYLIDENEACETALDEHYDES Manganese dioxide. CYCLOPENTANONES Magnesium. 1-Phenylthiocyclopropyltriphenylphosphonium fluoroborate. Simmons Smith reagent. Sodium tetracarbonylferrate(-II). CYCLOPENTENONES 3-Benzyl-5-(2-hydroxyethyl)-4-methyl-l,3-thiazolium chloride. Boron trifluoride etherate. Lithium dimethoxyphosphinylmethylide. Silver tetra-fluoroborate. Titanium tetrachloride. Triethyl phosphite. Vinyl triphenylphos-phonium bromide. 

The catalyst, 3-benzyl-5-(2-hydroxyethyl )-4-methyl-l, 3-thiazoHum chloride, is supplied by Fluka AG, Buchs, Switzerland, and by Tridom Chemical, Inc., Hauppauge, New York. The thiazolium salt may also be prepared as described below by benzylation of 5-(2-hydroxyethyl)-4-methyl-l,3-thiazole which is commercially available from E. Merck, Darmstadt, West Germany, and Columbia Organic Chemicals Co., Inc., Columbia, SC. The acetonitrile used by the checkers was dried over Linde 3A molecular sieves and distilled under nitrogen, bp 77-78°C. The same yield of thiazolium salt was obtained by the checkers when benzyl chloride and acetonitrile from commercial sources were used without purification. 

The use of thiazolium salts enables the benzoin condensation to proceed at room temperature. It can also be performed in dipolar aptotic solvents or under phase transfer conditions. Thiazolium salts such as vitamin Bi, thiazolium salts attached to y-cyclodextrin, macrobicyclic thiazolium salts, thiazolium carboxylate, ° naphtho[2,l-d]thiazolium and benzothiazolium salts catalyze the benzoin condensation and quaternary salts of 1-methylbenzimidazole and 4-(4-chlorophenyl)-4//-1,2,4-triazole are reported to have similar catalytic activity. Alkylation of 2-hydroxyethyl-4-methyl-l,3-thiazole with benzyl chloride, methyl iodide, ethyl bromide and 2-ethoxyethyl bromide yields useful salts for catalyzing 1,4-addition of aldehydes to activated double bonds. Insoluble polymer-supported thiazolium salts are catalysts for the benzoin condensation and for Michael addition of aldehydes. Electron rich al-kenes such as bis(l,3-dialkylimidazolidin-2-ylidenes) bearing primary alkyl substituents at the nitrogen atoms or bis(thiazolin-2-ylidene) bearing benzyl groups at the nitrogen atoms are examples of a new class of catalyst for the conversion of ArCHO into ArCHOHCOAr. 

J"Baaiy l-5-(2-hydroxyethy l)-4-methyl-1,3-thiazoliian chloride, 6, 38 39, 289 7, 16-17. Detailed directions are available for preparation of this thiazolium salt,1 which ll alio commercially available (Fluka). Examples of use of this catalyst in Oombination with triethylamine for acyloin condensation are cited. The heterocyclic hiroin can also be prepared with this catalyst. Synthesis of benzoins, however, requires use of a related catalyst, one substituted with an N-methyl or N-ethyl group In place of N-benzyl. 

This salt is prepared by reaction of 4-methyl-l,3-thiazole with benzyl chloride. Cyclic orketols. The benzoin-like condensation has been extended to a synthesis of cyclic a-ketols by condensation of pentane- and hexanedials with this thiazolium salt. Oxidation of the products results in 2-hydroxy-2-enones. Examples ... 

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