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【结 构 式】 
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【分子编号】33443 【品名】2,4-dichlorobenzoic carboxylic acid; 2,4-dichlorobenzoic acid 【CA登记号】50-84-0 |
【 分 子 式 】C7H4Cl2O2 【 分 子 量 】191.01296 【元素组成】C 44.02% H 2.11% Cl 37.12% O 16.75% |
合成路线1
该中间体在本合成路线中的序号：(I)The sulfonation of 2,4-dichlorobenzoic acid (I) with chlorosulfonic acid (II) at 140 C gives 5-chlorosulfonyl-2,4-dichlorobenzoic acid (III), which by reaction with liquid NH3 is converted into 5-sulfamoyl-2,4-dichlorobenzoic acid (IV). Finally, this compound is treated with NaOH.
| 【1】 Flueckiger, E.; Lindenmann, A.; Taeschler, M.; Schenker, E.; Jucker, E.; Synthetic drugs, XII. Constitution and salidiuretic effect of 3-sulfamoyl-4-chlorobenzoic acid derivatives and related compounds. Arzneim-Forsch Drug Res 1963, 13, 4, 269-280. |
| 【2】 Stephenson, O.; Wild, A.M.; Petrow, V.; Jackman, G.B.; Diuretic agents. VI. Some sulfamoylbenzoic acids. J Pharm Pharmacol 1962, 14, 679-686. |
| 【3】 Rusching, H.; Siedel, W.; Sturm, K.; Weyer, R.; Chemistry of furosemide. I. Syntheses of 5-sulfamoylanthranilic acid derivatives. Chem Ber 1966, 99, 1, 328-344. |
| 【4】 Hopkins, S.J.; Castaner, J.; Serradell, M.N.; Blancafort, P.; M-12,325. Drugs Fut 1983, 8, 3, 206. |
| 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) | 33443 | 2,4-dichlorobenzoic carboxylic acid; 2,4-dichlorobenzoic acid | 50-84-0 | C7H4Cl2O2 | 详情 | 详情 |
| (II) | 35975 | 2,4-dichloro-5-(chlorosulfonyl)benzoic acid | C7H3Cl3O4S | 详情 | 详情 | |
| (III) | 35976 | 5-(aminosulfonyl)-2,4-dichlorobenzoic acid; 2,4-Dichloro-5-sulfamoylbenzoic acid; lassamide | 2736-23-4 | C7H5Cl2NO4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)By condensation of 2,4-dichlorobenzoic acid (I) with anthranilic acid (II) by means of K2CO3, powdered Cu and a small amount of I2 in refluxing isoamyl alcohol.
| 【1】 Tanemura, M.; et al.; Aminobenzoesaurederivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel. BE 0842832; DE 2526092; JP 52012141 . |
| 【2】 Tomcufcik, A.S.; Dusza, J.P.; Albright, J.D.; Beer, B. (Wyeth); N-Methyl-N-(-[3-[-2-thienylcarbonyl]-pyrazol-[1,5-alpha]-pyrimidin-7-yl]phenyl)acetamide and compsns. and methods related thereto. US 6399621 . |
合成路线3
该中间体在本合成路线中的序号：(III)The reaction of 2,4-dichlorophenyl bromide (I) with 14CO2 (II) by means of BuLi in ethyl ether gives the labeled 2,4-dichlorobenzoic acid (III), which is reduced with LiAlH4 in the same solvent to yield 2,4-dichlorobenzyl alcohol (IV). The oxidation of (IV) with lead tetraacetate affords 2,4-dichlorobenzaldehyde (V), which is condensed with sodium sulfite in water at 160 C in a pressure vessel to provide the disulfonate (VI). Finally, the aldehyde group of (VI) is condensed with N-tert-butylhydroxylamine (VII) in hot acetic acid to give rise to the target imine oxide.
| 【1】 Johansson, R.; Werner, R.; Syntheses of two [14C]-labeled disodium 4-[(N-tert-butylimino)methyl]benzene-1,3-disulfonate N-oxides. J Label Compd Radiopharm 2000, 43, 13, 1265. |
| 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) | 53307 | 1-Bromo-2,4-dichlorobenzene | 1193-72-2 | C6H3BrCl2 | 详情 | 详情 |
| (III) | 33443 | 2,4-dichlorobenzoic carboxylic acid; 2,4-dichlorobenzoic acid | 50-84-0 | C7H4Cl2O2 | 详情 | 详情 |
| (III) | 53308 | 2,4-dichlorobenzoic acid | 50-84-0 | C7H4Cl2O2 | 详情 | 详情 |
| (IV) | 53309 | (2,4-dichlorophenyl)methanol | 1777-82-8 | C7H6Cl2O | 详情 | 详情 |
| (IV) | 53310 | 2,4-Dichlorobenzyl alcohol | 1777-82-8 | C7H6Cl2O | 详情 | 详情 |
| (V) | 22196 | 2,4-dichlorobenzaldehyde | 874-42-0 | C7H4Cl2O | 详情 | 详情 |
| (V) | 53311 | 2,4-dichlorobenzaldehyde | 874-42-0 | C7H4Cl2O | 详情 | 详情 |
| (VI) | 37311 | Benzaldehyde-2,4-disulfonic acid disodium; disodium 4-formyl-1,3-benzenedisulfonate | 33513-44-9 | C7H4Na2O7S2 | 详情 | 详情 |
| (VI) | 53312 | disodium 4-formyl-1,3-benzenedisulfonate | 119557-95-8 | C7H4Na2O7S2 | 详情 | 详情 |
| (VII) | 36455 | (1R,12S)-9-hydroxy-8-methyl-4,6,14-trioxa-16-azatetracyclo[10.3.1.0(2,10).0(3,7)]hexadeca-2,7,9-trien-13-one | C13H13NO5 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(V)2,4-Dichlorobenzoic acid (V) was converted to acid chloride (VI) using SOCl2. Further Friedel-Crafts condensation of (VI) with toluene in the presence of AlCl3 produced benzophenone (VII). Benzylic bromination of (VII) with N-bromosuccinimide gave bromide (VIII). Finally, displacement of the bromine of (VIII) by means of amine (IV) furnished the title compound.
| 【1】 Zhou, Y.; Zhang, W.; Li, K.; Jiang, Y.; Li, Y.; Wang, X.; The synthesis and antifungal activity of the substituted naphthalenemethanamines. Chin Journal of Medicinal Chemistry 1999, 9, 7, 7. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 10108 | N-Methyl(1-naphthyl)methanamine; N-Methyl-N-(1-naphthylmethyl)amine; 1-Methyl-1-naphthalenemethylamine | 65473-13-4 | C12H13N | 详情 | 详情 |
| (V) | 33443 | 2,4-dichlorobenzoic carboxylic acid; 2,4-dichlorobenzoic acid | 50-84-0 | C7H4Cl2O2 | 详情 | 详情 |
| (VI) | 35131 | 2,4-dichlorobenzoyl chloride; 2,4-Dichlorophenacylchloride | 89-75-8 | C7H3Cl3O | 详情 | 详情 |
| (VII) | 35132 | (2,4-dichlorophenyl)(4-methylphenyl)methanone | C14H10Cl2O | 详情 | 详情 | |
| (VIII) | 35133 | [4-(bromomethyl)phenyl](2,4-dichlorophenyl)methanone | C14H9BrCl2O | 详情 | 详情 |