CS276701B6 - Trimethoxystyrenes and process for preparing thereof - Google Patents

Abstract

Trimethoxystyrenes of Formula I are by intramolecular elimination of water from the respective secondary trimethoxyphenyl- Efcylalcohol of formula II, which is it is gradually added to the refluxing solvent in the presence of anhydrous copper sulfate with the addition of a polymerization inhibitor, refluxing for 5 hours, nero-depleted the component is separated, the solution is concentrated and subsequently distilled.

Description

The invention relates to styrene derivatives characterized by the presence of three methoxyl groups on the benzene nucleus and to a process for their preparation by dehydration of the corresponding trimethoxyphenylethyl alcohols.

Trimethoxystyrenes substituted by a methoxyl radical in position 2,3,4 as well as 2,4,5 have not yet been prepared. Analogous compounds were prepared by intramolecular cleavage of water from the appropriate trimethoxyphenylethyl alcohols. in the presence of acid catalysts (Organic Syntheses, 3, 1955, C. G. Overberger, 3. H. Saunders, m-Chlorstyrene, Ed. John Wiley et Sons, Inc., New York, pp. 204-206). This method has not been reproduced by W. Kleeberg and G. Suchardt (Naturwiss., 44, 1957, W. Kleeberg, G. Suchardt, Observations on Dehydration of Arylmethylcarbinols, p. 584), who moreover deny the suitability of the use of acidic acids. dehydration catalysts, since the corresponding formation of the corresponding diaryl ethers takes place under such conditions, as is the case with methoxylated styrenes.

The invention relates to trimethoxystyrenes of the formula I

OCH 2 where the radicals and R 1 are different, represent H or CH 2 O, these radicals R 1 and R 2 being substituted in position 3, 5.

Furthermore, the process for the preparation of trimethoxystyrenes of the formula I according to the invention is based on the fact that the secondary trimethoxyphenylethyl alcohol of the formula CH-OH

OCH 2 where R 1 and R 2 are as defined above, are treated with a refluxing solvent boiling at 140 DEG-174 DEG C. in the presence of anhydrous copper sulfate, optionally with the addition of a polymerization inhibitor, refluxed for 15 minutes to 4 hours, the insoluble component separated, the solution it is concentrated and subsequently distilled at a pressure of 20 to 100 Pa. Nonane, propylbenzene or decane are used as the refluxing solvent with a boiling point between 151 and 174 ° C.

According to the invention, the secondary trimethoxyphenylethyl alcohol is dehydrated intramolecularly, the reaction being easily controlled by determining the amount of water in the separator. Yields are up to 75% for 2,3,4-trimethoxystyrene. If the trimethoxystyrenes obtained are not used as an intermediate within 48 hours, they must be stabilized by the addition of a polymerisation inhibitor, from which they can be separated by distillation at a pressure of 20 to 100 Pa before use.

Examples of embodiments of the invention

Example 1

Pour 100 ml of dean and 1.6 g of anhydrous copper sulphate into a 250 ml flask equipped with mechanical stirring, a dropping funnel with an elongated stem and a water separator with a poor condenser, placed in a laboratory heating nest and add 1.6 g of anhydrous copper sulphate. It is refluxed for 10 minutes at a boiling point of decane of 174 ° C, during which time water is removed via a separator if copper sulphate contains traces of water. Then 53 g (0.25 mol) of 1- (2,3,4-tri) are added dropwise

(Methoxyphenyl) ethyl alcohol for: 15 minutes and heating is maintained at a constant reflux throughout the reaction time. The reaction is stopped when no more water is excreted. The insoluble component is filtered off from the reaction mixture, the filtrate is concentrated at a pressure of 0.5 kPa and the crude product is distilled off at a pressure of up to 60 Pa. The purity of the product is checked by thin-layer chromatography in a solvent system of ethyl acetate with benzene in a volume ratio of 1: 3, visibility of the spots with iodine vapor. The retention factor Rf is 0.85 for 2,3,4-trimethoxystyrene, 0.25 for 1- (2,3,4-trimethoxyphenyl) ethyl alcohol and 0.60 for diaryl ethers. 2,3,4-Trimethoxystyrene is obtained in 75% yield (0.19 mol), in the form of a syrup with a boiling point of 78-81 ° C at a pressure of 27 Pa. On the proton nuclear magnetic resonance spectrum of 1 H-NMR, these are the determining peaks; 3.82, 3.86, 3.89, 5.15, 5.59, 6.49, 6.98 and 7.00.

Elemental analysis for molecular weight 194 194.23, molecular weight ’determined by mass spectrum 194 calculated: 67.96 wt. % carbon, 7.27 wt. % hydrogen, found: 67.14 wt. % carbon, 6.82 wt. % hydrogen.

Example 2

The procedure is as in Example 1, except that nonane is used as the solvent at a boiling point of 151 DEG C. and 1- (2,4,5-trimethoxyphenyl) ethyl alcohol, and 0.1% by weight is added to the reaction mixture. % of p-tert-butylpyrocatechin based on the theoretical amount of 2,4,5-trimethoxystyrene formed as polymerization inhibitor. 2,4,5-Trimethoxystyrene is obtained in 25% yield (0.06 mol) in the form of yellowish lumps with a melting point of 50-55 ° C, a boiling point of 112-116 ° C at a pressure of 53 Pa. On the proton magnetic resonance spectrum 1 H-NMR, the following determining peaks are: 3.82, 3.89, 5.15, 5.59, 6.49, 6.98 and 7.00.

Elemental analysis for θχ ^ Η ^ Ο ^, molecular weight 194.23, molecular weight determined by mass spectrum 194 calculated: 67.96 wt. % carbon, 7.27 wt. % hydrogen, found: 67.14 wt. % carbon, 6.82 wt. % hydrogen.

The novel trimethoxystyrenes prepared by the process of the invention are important intermediates for the preparation of styrene oxides as well as biologically active azarone and adrenaline derivatives which have utility in biochemistry, molecular biology, medical sciences such as e.g. model substances in the study, transmission of nerve impulses by the adrenergic system.

Claims (3)

Methoxyphenyl ethyl alcohol for 15 minutes and constant reflux is maintained over the entire reaction time. The reaction is stopped when water is excreted. The insoluble component is filtered off from the reaction mixture, the filtrate is concentrated at 0.5 kPa and the crude product is distilled at a pressure of up to 60 Pa. The purity of the product is checked by thin-layer chromatography in a solvent system of ethyl acetate with benzene in a volume ratio of 1: 3, visualization of the stains with iodine vapors. The retention factor Rf is 0.85 for 2,3,4-trimethoxystyrene, 0.25 for 1- (2,3,4-trimethoxyphenyl) ethyl alcohol and 0.60 for diaryl ethers. 2,3,4-Trimethoxystyrene is obtained in 75% yield (0.19 mol) as a syrup having a boiling point of 78-81 ° C at a pressure of 27 Pa. On the proton nuclear magnetic resonance spectrum, @ 1 H-NMR, these determining peaks are 3.82, 3.86, 3.89, 5.15, 5.59, 6.49, 6.98, and 7.00. Elemental analysis for molecular weight 194.23, molecular weight determined by mass spectrum 194 calculated: 67.96 wt. % carbon, 7.27 wt. % hydrogen, found: 67.14 wt. % carbon, 6.82 wt. % hydrogen. EXAMPLE 2 The procedure of Example 1 was followed except that the nonane was used as the solvent at 151 DEG C. and the 1- (2,4,5-trimethoxyphenyl) ethyl alcohol was added and 0.1 wt. % of p-tert-butylpyrocatechin based on the theoretical amount of 2,4,5-trimethoxystyrene formed as polymerization inhibitor. 2,4,5-Trimethoxystyrene is obtained in a 25% yield (0.06 mol) in the form of yellowish lumps with a melting point of 50 DEG-55 DEG C., 112 DEG-116 DEG C. at a pressure of 53 Pa. On the proton magnetic resonance spectrum, @ 1 H-NMR, the following peaks are determined: 3.82, 3.09, 5.15, 5.59, 6.49, 6.98 and 7.00. Elemental analysis for the title compound, molecular weight 194.23, molecular weight determined by mass spectrum 194 calculated: 67.96 wt. % carbon, 7.27 wt. % hydrogen, found: 67.14 wt. % carbon, 6.82 wt. % hydrogen. The novel trimethoxystyrenes prepared according to the invention are important intermediates for the preparation of styrene oxides, as well as biologically active derivatives of azarone and adrenaline, which have utility in biochemistry, molecular biology, medical science such as modeling in the study, transmission of nerve excitement by the adrenergic system. PATENT CLAIMS 1. Trimethoxystyrenes of general formula I wherein the radicals R 1 and R 6 are different, represent H or CH-10, these radicals R 1 and R 6 is substituted at the 3,5 position. 2. A process for the preparation of trimethoxystyrenes of general formula I according to claim 1, characterized in that the trimethoxyphenylethyl alcohol of general formula II 3 CS 276701 B 6 CH, I 3 where and R 'are as defined above, a refluxing solvent of boiling temperature of 151 to 174 ° C is applied in the presence of anhydrous copper sulfate, optionally with the addition of a polymerization inhibitor, refluxing for 15 minutes to 4 hours, the insoluble component is separated off, the solution is concentrated and subsequent distillation at a pressure of 20 to 100 Pa. 3. A process for the preparation of trimethoxystyrenes of formula (I) according to claim 2, wherein the refluxing solvent is a solvent having a boiling point of from 151 DEG to 174 DEG C., preferably a nonane, a propylbenzene or a decane.