Chemistry of thiazole, I. Synthesis and properties of 2,3,5,6‐tetrahydro‐6‐(3‐methylbenzofuran‐2‐yl)imidazo[2,1‐ b ]thiazole

Abstract

Chemie des Thiazols, ISynthese und Eigenschaften von 2,3,5,6-Tetrahydro-6-(3-methylbenzofuran-2-~I)-irnidazoI2,1-bJthiazolx) Die Titelverbindung 13 wird auf zwei Wegen ausgehend von 2-Hydroxyacetophenon (1) iiber das Benzofuran-Derivat 7 und die Thiazolidine 9 bzw. 10 erhalten.In search of new biologically active compounds the synthesis of heterocyclic analogues of tetramisole * ) has been undertaken. The present paper describes the synthesis of the title compound 13 not known in the literature. 2-Bromo-l-(3-methylbenzofuran-2-yl)ethanone (7), prepared in two ways, was the key compound. In both methods, 2-hydroxyacetophenone (1) was used as the starting substance. 1 reacts with chloroacetone in the presence of anhydrous K,CO, in acetone to yield 4. In a second way, from the reaction of 1 with ethyl chloroacetate under the same conditions ethyl (2-acety1phenoxy)acetate (2) was obtained in 58% yield. Its basic hydrolysis gave (2-acetylphenoxy)acetic acid (3). This acid was cyclized in the presence of acetic anhydride and sodium acetate to 3-methylbenzofuran (5) in 62% yield. Hydrocarbon 5, when treated with acetyl chloride in the presence of anhydrous AICI, in CS,, formed 4 (52'70), identical with the substance obtained above.Ethanone 7 was prepared also in two ways. In the first method, ketone 4 was brominated using the complex of bromine and dioxane in anhydrous ether. In the second way, 7 was obtained on direct treating of hydrocarbon 5 with BrCH,COCI in the presence of anhydrous AICI, in CS, (52%). The second component for the preparation of the title compound, i. e. 2-iminothiazolidine (6), was obtained from thiourea solution by treating with ethylenimine in 50% H,SO,. This compound exists in equilibrium with its tautomeric form 2-amino-2-thiazoline (6a).Condensation of w-bromoketone 7 with 6 leads to the 3-substituted derivative 8 of thiazolidine as hydrobromide in 96% yield. Hydrobromide 8 was decomposed yielding ketone 9, the imine function of which was blocked by acetylation to give 12. Reduction of 12 with NaBH, in methanol resulted in the formation of the ethanol derivative 14, which was treated with thionyl chloride in CHCI,. The resulting crude chloride was then cyclized with K,CO, in water and the obtained title compound 13 was purified via its hydrochloride 11.

Preparation of Highly Functionalised Benzofurans from ortho‐Hydroxyphenones and Dichloroethylene: Applications and Mechanistic Investigations

“…Using our methodology, nerolione 39 was readily assembled as shown in Scheme . However, our spectroscopic data did not match those reported in the literature 35. Therefore, to establish unambiguously the structure of our compound, the corresponding oxime 40 was prepared and crystallised.…”

“…However, our spectroscopic data did not match those reported in the literature. [35] Therefore, to establish unambiguously the structure of our compound, the corresponding oxime 40 was prepared and crys-tallised. A single-crystal X-ray diffraction analysis confirmed our assignment (Scheme 20); the previous data in the literature are thus incorrect.…”

Microwave Assisted Synthesis of Novel Functionalized Hydantoin Derivatives and Their Conversion to 5-(Z) Arylidene-4H-imidazoles

“…Since the starting material for 2b is not commercially available, it was prepared according to the literature procedure [ 11 , 12 ] which involved converting 2-hydroxy acetophenone to 3-methylbenzofuran [ 11 ] which was subsequently transformed to benzofuran-3-carbaldehyde by refluxing with SeO 2 in 1,4-dioxane [ 12 ].…”

Synthesis, Absolute Configuration, Antibacterial, and Antifungal Activities of Novel Benzofuryl β-Amino Alcohols

“…Boni Protect ® from Koppert Biological Systems (Vienna, Austria) contains germinating fungal Aureobasidium pullulans DSM 14940 and 14941 strains (500 g per 1 kg of the preparation). 1-(Benzofuran-2-yl)-2-bromoethanone ( 1 ) [ 45 ], 2-bromo-1-(7-ethylbenzofuran-2-yl)ethanone ( 2 ) [ 46 ], 2-bromo-1-(3-methylbenzofuran-2-yl)-ethanone ( 3 ) [ 47 ], [(( R , R )-2-Amino-1,2-diphenylethyl)[(4-tolyl)sulfonyl]amido](chloro)pentamethylcyclopentadienylrhodium(I) (RhCl[( R , R )-TsDPEN](C 5 Me 5 )) [ 48 ] were prepared according to the literature. 2-Bromo-1-(3,5-dimethylbenzofuran-2-yl)ethanone ( 4 , mp 82–84 °C, 1 H NMR (700 MHz, CDCl 3 ) δ (ppm): 2.50 (s, 3H, CH 3 ), 2.63 (s, 3H, CH 3 ), 4.53 (s, 2H, CH 2 ), 7.35 (dd, 1H, J = 8.4 Hz, J = 1.4 Hz, CH), 7.42 (d, 1H, J = 9.1 Hz, CH), 7.46–7.47 (m, 1H).…”