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【结 构 式】 
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【分子编号】39985 【品名】4-hydroxy-3,5-dimethylbenzaldehyde；3,5-Dimethyl-4-hydroxybenzaldehyde 【CA登记号】2233-18-3 |
【 分 子 式 】C9H10O2 【 分 子 量 】150.1772 【元素组成】C 71.98% H 6.71% O 21.31% |
合成路线1
该中间体在本合成路线中的序号：(II)The reaction of 2,6-dimethylphenol (I) with hexamethylenetetramine (HMT) and sulfuric acid in ethyleneglycol at 130 C gives 4-hydroxy-3,5-dimethylbenzaldehyde (II), which is finally condensed with 2-(2-thienyl)acetic acid (III) by means of piperidine in dichloromethane at 130 C.
| 【1】 Lazer, E.S.; Farina, P.R.; Gundel, R.H.; Wegner, C.D.; 2,6-Disubstituted-4-(2-arylethenyl)phenol 5-lipoxygenase inhibitors: Development and profile of BI-L-239. Drugs Fut 1991, 16, 7, 641. |
合成路线2
该中间体在本合成路线中的序号：(II)The reaction of 2,6-dimethylphenol (I) with hexamethylenetetramine (HMT) and sulfuric acid in ethyleneglycol at 130 C gives 4-hydroxy-3,5-dimethylbenzaldehyde (II), which is finally condensed with 2-(4-fluorophenyl)acetic acid (III) by means of piperidine in dichloromethane at 130 C.
| 【1】 Lazer, E.S.; Farina, P.R.; Gundel, R.H.; Wegner, C.D.; 2,6-Disubstituted-4-(2-arylethenyl)phenol 5-lipoxygenase inhibitors: Development and profile of BI-L-239. Drugs Fut 1991, 16, 7, 641. |
合成路线3
该中间体在本合成路线中的序号：(III)5,6-Dimethoxy-1-indanone (I) was selectively nitrated at position 7 by means of NaNO2 in trifluoroacetic acid. Acid-catalyzed aldol condensation of the resulting nitroindanone (II) with 3,5-dimethyl-4-hydroxybenzaldehyde (III) afforded the E-unsaturated ketone (IV). Finally, reduction of the nitro group of (IV) with either sodium dithionite or zinc dust and AcOH yielded the corresponding amino derivative.
| 【1】 Shih, H.; Carson, D.A.; Deng, L.; Carrer, C.J.; Cottam, H.B.; Adachi, C.J.; Rational design, synthesis and structure-activity relationships of antitumor (E)-2-benzylidene-1-tetralones and (E)-2-benzylidene-1-indanones. Bioorg Med Chem Lett 2000, 10, 5, 487. |
| 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) | 13430 | 5,6-Dimethoxy-1-indanone; 2,3-Dihydro-5,6-dimethoxy-1H-inden-1-one | 2107-69-9 | C11H12O3 | 详情 | 详情 |
| (II) | 39984 | 5,6-dimethoxy-7-nitro-1-indanone | C11H11NO5 | 详情 | 详情 | |
| (III) | 39985 | 4-hydroxy-3,5-dimethylbenzaldehyde；3,5-Dimethyl-4-hydroxybenzaldehyde | 2233-18-3 | C9H10O2 | 详情 | 详情 |
| (IV) | 39986 | 2-[(E)-(4-hydroxy-3,5-dimethylphenyl)methylidene]-5,6-dimethoxy-7-nitro-1-indanone | C20H19NO6 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)Aldol condensation of 4’-(methylthio)acetophenone (I) with 4-hydroxy-3,5-dimethylbenzaldehyde (II) in the presence of HCl in EtOH yields chalcone (III), which is then alkylated with isopropyl α-bromoisobutyrate (IV) using K2CO3 in refluxing acetonitrile to give ether (V). Finally, isopropyl ester (V) is hydrolyzed using TFA in CH2Cl2 .
| 【1】 Najib, J., Caumont-Bertrand, K. (Genfit SA). Substituted 1,3-diphenylprop-2-en-1-one derivatives, preparation and uses thereof. CA 2490986, EP 1525177, FR 2841900, JP 2005532385, US 2005176808, US 200703243, US 7566737, US 7943661, US 2011190515, US 8058308, WO 2004005233. |
| 【2】 Delhomel, J.-F., Caumont-Bertrand, K. (Genfit SA). Preparation of 1,3-diphenylprop-2-en-1-one derivatives. CA 2531443, CN 1818986, EP 1644312, FR 2857361, JP 2007516189, US 2006142611, US 7385082, WO 2005005369. |
| 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) | 19262 | 1-[4-(methylsulfanyl)phenyl]-1-ethanone；4'-Methylthioacetophenon；4’-(methylthio)acetophenone | 1778-09-2 | C9H10OS | 详情 | 详情 |
| (II) | 39985 | 4-hydroxy-3,5-dimethylbenzaldehyde；3,5-Dimethyl-4-hydroxybenzaldehyde | 2233-18-3 | C9H10O2 | 详情 | 详情 |
| (III) | 68545 | (E)-3-(4-hydroxy-3,5-dimethylphenyl)-1-(4-(methylthio)phenyl)prop-2-en-1-one | C18H18O2S | 详情 | 详情 | |
| (IV) | 68546 | isopropyl α-bromoisobutyrate；Isopropyl 2-bromo-2-methylpropanoate | 51368-55-9 | C7H13BrO2 | 详情 | 详情 |
| (V) | 68547 | (E)-isopropyl 2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxoprop-1-en-1-yl)phenoxy)-2-methylpropanoate | C25H30O4S | 详情 | 详情 |