4- Methyl-l,3-thiazole

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. 

An important biological process is the basis for a general coupling method of aldehydes into symmetncal acyloins, such as BETYROIN. The key catalyst is 5-(2-hydroxyethyl)-4-methyl-l,3-thiazole, an analog of thiamin. Condensation of ketones and aldehydes with excess acetonitrile can be accomplished in a simple way to produce a,p-unsaturated nitriles Cyclohexanone leads to CY-CLOHEXYLIDENEACETONITRILE while benzaldehyde gives CINNA-MONITRILE. 

A 250-mL, three-necked, round-bottomed flask is equipped with a mechanical stirrer, a reflux condenser fitted with a drying tube, and a stopper. The flask is charged with 14.3 g (0.1 mol) of 5-(2-hydroxyethyl)-4-methyl-l,3-thiazole, 12.7 g (0.1 mol) of freshly distilled benzyl chloride, and 50 mL of dry acetonitrile. The mixture is heated at reflux for 24 hr and cooled to room temperature. Crystallization is induced by scratching or seeding. The solid is collected by suction filtration, washed colorless with two 50-mL portions of acetonitrile, and dried partially in the air. Drying is... 

Benzyl-5-(2-hydroxyethyl)-4-methyl-l,3-thiazol 1um chloride is supplied by Fluka AG, Buchs, Switzerland and by Tridom Chemical, Inc., Hauppague, New fork. The thiazolium salt may also be prepared as described in Org. Synth. 1984, 42, 170. 

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. 

Amlno-5-ethoxycarbonyl-4-methyl-l,3-thiazol (R1 = CH, R2 = COOC2H< R CHj)93 (Methode ) Zu... 

N- -CH3 c6hs Br Ethanol Riickfl. 1 2-( 4-Methyl-l, 3-thiazol-2-ylamino )- 90 245 353... 

Amino-5-(2-hydroxy-ethyl)-4-methyl-l,3-thiazol-Hydrochlorid (R1 = CH3 R2 = CH2—CH2—OH)159 Eine Mischung von 45,6 g (0,6 mol) Thioharnstoff und 81,6 g (0.6 mol) 3-Chlor-5-hydroxy-2-oxo-pentan in 600 ml Wasser wird unter RuckfluB erhitzt. Nach dem Abkiihlen wird die Losung mit Diethylether ge-waschen. Man dampft die waBr. Phase ein. Der Riickstand wird i. Vak. (5 Torr/0,67 kPa) bei 60° getrocknet und aus Aceton/Ethanol umkristallisiert Ausbeute 73 g (77%) Schmp. 156-157°. 

CO-NH-C6H5 ch3 Cl Cl Ethanol Ruckfl. 10 2- ( Anilinocarbony lamina )-5-chlor-4-methyl-l, 3-thiazol 56 222 337... 

Amino-4-methyl-l,3-thiazol (R1 = CH3)664 In eine Losung von 3,2 g (0,04 mol) 2-Isocyan-propansaure-nitril und 4 g (0,04 mol) Tricthylamin in 20 ml Dichlormethan wird unter kraftigem Riihren 45 min Schwefelwasserstoff cingeleitet. Das Losungsmittel wird i. Vak. abgezogen Ausbeute 3,4 g (75%) Schmp. 91°. 

Acetj l-2-amino-4-methyl-l,3-thiazol (R1 = NH2 R2 = CO—CH3)617 lg (0,0064 mol) 2-Amino-4-oxo-3-thiocyanat-2-penten werden in 10m/ IN methanol. Kalilauge 3 min zum Sieden erhitzt. Schon in der Hitze fallen Kristalle aus. Nach Abdestillieren des Methanols wird mit Wasser versetzt. Das Endprodukt wird abgesaugt Ausbeute 0,96 g (96%) Schmp. 265-266°. 

Aminocarbonyl-phenylhydrazono-methyl) -5-ethoxycar bonyl-4-methyl l,3-thiazol, 63% Schmp.r 215-217°... 

Die N-Alkylierung von 4-Methyl-l,3-thiazol eignet sich auch zur Einfuhrung von Cyclophan-Resten fiir die Herstellung von Enzym-Modellen1234. 

Acetoxy-niethyl)-l,3-thiazoI1021 Einc Mischung von 3,5 g (0,03 mol) 4-Methyl-l,3-thiazol 3-oxid und 18 m/ Acetanhydrid wird 10 min unter RlickfluB erhitzt. AnschlieBend werden die niedriger siedenden Bestandteile entfernt und der Riickstand i. Vak. destilliert Ausbeute 2,7 g (56%), Sdp 76J/1 Torr (0,13 kPa). 

Wahrscheinlich handelt es sich bei dem Umsetzungsprodukt von 2,4-Dimethyl-1,3-thiazol mit waBrigem Formaldehyd nicht, wie angegeben1508, um 4-(2-Hydroxy-ethyl)-l,3-thiazol, sondern um 2-(2-Hydroxy-ethyl)-4-methyl-l,3-thiazol. 

Aus 2-Benzyl-4-methyl-l,3-thiazol bzw. Bis-[l,3-thiazol-4-yl]-methan entstehen durch Oxidation mit Selendioxid 2-Benzoyl-4-methyl-l,3-thiazol1225 (75%) bzw., 3-thiazol-4-yl]-ke-ton1120 (25 50%). 

Zur Herstellung der Ketone aus den entsprechcndcn sekundaren Alkoholen s. Bd. VI l/2a, S. 725. 4-Cyan-1,3-thiazol wird durch Ammonoxidation von 4-Methyl-l,3-thiazol erhalten ... 

Bis-[(5-cthoxycarbonyl-4-methyl-l, 3-thiazol-2-yl)-hydrazono]-5,5 -bi-(2,5-dihydro-l, 3-thiazolylidenc)347... 

Bis-[l,3-Benzothiazol-2-ylthio]-organo- 997 Bis-[4-tert.-butyl-1,3-thiazol-2-yl]- 71 Bis-[l,3-dimethyl-lH-pyrazol-5-yl]- 557 Bis-[4,5-diphenyl-l,3-thiazol-2-yl]- 71 Bis-[4-methyl-l,3-thiazol-2-yl]- 71 Bis-[5-nitro-l,3-thiazol-2-yl]- 244 Bis-[l,3-thiazol-2-yl]- 70, 71 Ethyl- 337... 

Bis-[4-amino-2-methylthio-l,3-thiazol-5-yl]- 138 Bis-[2-dimethylamino-4-methyl-l,3-thiazol-5-yl]- 133... 

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