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【结 构 式】 
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【分子编号】21238 【品名】4-(methylsulfanyl)benzoyl chloride 【CA登记号】 |
【 分 子 式 】C8H7ClOS 【 分 子 量 】186.66168 【元素组成】C 51.48% H 3.78% Cl 18.99% O 8.57% S 17.18% |
合成路线1
该中间体在本合成路线中的序号：(II)The reaction of 4-(methylthio)benzoic acid (I) with SOCl2 in refluxing benzene gives 4-(methylthio)benzoyl chloride (II), which is then condensed with 1,3-dihydro-4-methyl-2H-imidazol-2-one (III) by means of AlCl3 in hot nitrobenzene.
| 【1】 Dage, R.C.; Schnettler, R.A.; Grisar, J.M. (Aventis Pharmaceuticals, Inc.); 4-Aroylimidazol-2-ones. BE 0883856; DE 3021792; FR 2459233; GB 2055364; JP 56005463 . |
| 【2】 Pento, J.T.; Serradell, M.N.; Castaner, J.; Blancafort, P.; RMI-17,043. Drugs Fut 1983, 8, 4, 343. |
合成路线2
该中间体在本合成路线中的序号：(VII)The acylation of 2,3-dihydrobenzofuran (I) with acetyl chloride and AlCl3 in dichloromethane gives 5-acetyl-2,3-dihydrobenzofuran (II), which by reaction with sulfur, morpholine (III) and p-toluenesulfonic acid at high temperature yields 2-(2,3-dihydrobenzofuran-5-yl)thioacetic acid morpholide (IV). The hydrolysis of (IV) with H2SO4 in refluxing water-acetic acid affords 2-(2,3-dihydrobenzofuran-5-yl) acetic acid (V), which is esterified to (VI) with ethanol and H2SO4 in refluxing toluene. The condensation of the ester (VI) with 4-(methylthio)benzoyl chloride (VII) by means of SnCl4 in refluxing dichloromethane gives ethyl 2-[7-[4-(methylthio)benzoyl]benzofuran-5-yl]acetate (VIII), which by hydrolysis with NaOH in refluxing methanol-water yields the corresponding acid (IX). Finally, this compound is dehydrogenated with N-bromosuccinimide (NBS) and dibenzoyl peroxide in refluxing CCl4.
| 【1】 Dunn, J.P. [Syntex (Syntex (USA) LLC); Aroyl benzofuran and benzothiophene acetic and propionic acids, processes for their production and pharmaceutical compositions containing them. AU 8430593; EP 0132130; ES 8604554; ES 8607960; JP 85038376 . |
| 【2】 Prous, J.; Castaner, J.; TIFURAC SODIUM < Rec INNM; USAN >. Drugs Fut 1989, 14, 8, 775. |
| 【3】 Tomolonis, A.J.; Dunn, J.P.; Ackerman, N.A.; Analgetic and antiinflammatory 7-aroylbenzofuran-5-yl acetic acids and 7-aroylbenzothiophene-5-ylacetic acids. J Med Chem 1986, 29, 11, 2326. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 14499 | 2,3-Dihydrobenzofuran; 2,3-dihydro-1-benzofuran | 496-16-2 | C8H8O | 详情 | 详情 |
| (II) | 21233 | 1-(2,3-dihydro-1-benzofuran-5-yl)-1-ethanone | 90843-31-5 | C10H10O2 | 详情 | 详情 |
| (III) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
| (IV) | 21235 | 2-(2,3-dihydro-1-benzofuran-5-yl)-1-(4-morpholinyl)-1-ethanethione | C14H17NO2S | 详情 | 详情 | |
| (V) | 14500 | 2-(2,3-dihydro-1-benzofuran-5-yl)acetic acid | 69999-16-2 | C10H10O3 | 详情 | 详情 |
| (VI) | 21237 | ethyl 2-(2,3-dihydro-1-benzofuran-5-yl)acetate | C12H14O3 | 详情 | 详情 | |
| (VII) | 21238 | 4-(methylsulfanyl)benzoyl chloride | C8H7ClOS | 详情 | 详情 | |
| (VIII) | 21239 | ethyl 2-[7-[4-(methylsulfanyl)benzoyl]-2,3-dihydro-1-benzofuran-5-yl]acetate | C20H20O4S | 详情 | 详情 | |
| (IX) | 21240 | 2-[7-[4-(methylsulfanyl)benzoyl]-2,3-dihydro-1-benzofuran-5-yl]acetic acid | C18H16O4S | 详情 | 详情 |