CN102311351A - Synthesis method of 2, 4-dimethoxybenzylamine - Google Patents
Synthesis method of 2, 4-dimethoxybenzylamine Download PDFInfo
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- CN102311351A CN102311351A CN201110191750A CN201110191750A CN102311351A CN 102311351 A CN102311351 A CN 102311351A CN 201110191750 A CN201110191750 A CN 201110191750A CN 201110191750 A CN201110191750 A CN 201110191750A CN 102311351 A CN102311351 A CN 102311351A
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- dimethoxybenzylamine
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Abstract
The invention discloses a synthesis method of 2, 4-dimethoxybenzylamine, comprising two steps of: synthesis of 2, 4-dimethoxybenzylchloride, and adding of 2, 4-dimethoxybenzylchloride, sodium iodide and urotropine into a solvent A for stirring and reaction so as to synthesize 2, 4-dimethoxybenzylamine. The synthesis method of the intermediate 2, 4-dimethoxybenzylchloride has the reaction occur in a two-phase system, in the presence of quaternary onium salt of a catalytic amount and under mild reaction conditions. And a single chloromethylation product is of high selectivity. With easily available and cheap raw materials, the production cost of 2, 4-dimethoxybenzylamine is low. Also with mild reaction conditions, the method of the invention has safe and simple operation, high reaction yield, and fewer "three wastes" generated, thus being suitable for industrial production.
Description
Technical field
The present invention relates to a kind of 2, the compound method of 4-dimethoxybenzylamine.
Background technology
Aminated compounds is a very important midbody in the organic synthesis, and purposes is very extensive, particularly the design of medicine and spices and synthetic in crucial more.Amine and amide derivatives thereof are the most general functional groups in the medicine that register in the whole world, in comprehensive drug data base, all exist in 2/3rds the above medicine.And in spices, also all comprise amine and amide group in food spice such as a large amount of savory agents, coolant agent, freshener and the food flavouring.Therefore research and develop various amine and verivate is very significant important process.
2, the 4-dimethoxybenzylamine is exactly a kind of very important aminated compounds, promptly can do the raw material of various resin of industry and product, also is medicine and spices synthetic important intermediate.
The chloro thing is a kind of important synthesis intermediates, is that raw material can synthesize compounds such as various alcohol, aldehyde, amine with it.The chloromethylation of aromatic compound is used to synthetic chlorinated aromatic hydrocarbons usually.General chloromethylation general formula is as follows:
Aromatic compound 1 and has Lewis acid---be generally zinc chloride and make catalyzer---and formolite reaction to obtain the verivate 2 of chloromethylation in hydrogen chloride gas.Other Lewis acid is like boron trifluoride, and tin tetrachloride, iron trichloride etc. are also available.Acetic acid commonly used is as solvent (Synthesis November 1991 pp.1003-1004).
The yield of chloromethylation product depends on the generation of many chloromethylations by product 3 and diphenylmethane derivatives 4, because the Friedel-Crafts alkylated reaction also is acid catalyzed with same Lewis.The regioselectivity of product is not high, and is not easy control.
Also have report to point out that aromatic compound and methoxyacetyl chloride and aluminum chloride carry out chloromethylation in Nitromethane 99Min. or dithiocarbonic anhydride, yield is fine.The methyl-phenoxide compounds that particularly ortho para is had a strong electron-withdrawing group group is (Tetrahedron Letters, Vol.24, No.18, pp 1933-1936,1983) especially effectively.But by product 3 and 4 with the aromatic hydrocarbons that has the electron rich group has just been become primary product.
Summary of the invention
The objective of the invention is to provide a kind of 2, the compound method of 4-dimethoxybenzylamine in order to solve above-mentioned technical problem.
The technical scheme that the present invention adopts
A kind of compound 2, the general structure of 4-dimethoxybenzylamine is as shown in Figure 1.
Above-mentioned a kind of 2; The compound method of 4-dimethoxybenzylamine, its total synthetic route chart is as shown in Figure 2, comprise general structure as shown in Figure 32; The synthetic of 4-dimethoxy benzyl chlorine reaches 2; 4-dimethoxy benzyl chlorine and Soiodin, urotropine add in the solvent orange 2 A, stirring reaction Synthetic 2,2 steps such as 4-dimethoxybenzylamine.
Above-mentioned a kind of 2, the compound method of 4-dimethoxybenzylamine, its concrete building-up process comprises the following steps:
(1), 2,4-dimethoxy benzyl chlorine synthetic
Phenylene dimethyl ether, muriate and Paraformaldehyde 96 between in acidic solution, adding; Chloromethylation is carried out in heating under the catalysis of phase-transfer catalyst, and the reaction process controlled temperature is 60～120 ℃, is preferably 60～80 ℃; Time is 4h; Synthetic 2,4-dimethoxy benzyl chlorine, its building-up reactions synoptic diagram is as shown in Figure 4;
Wherein, described acid is a kind of in sulfuric acid, concentrated hydrochloric acid, the sulfonic acid, preferably sulfuric acid.
Described muriate is a kind of in phosphorus trichloride, phosphorus pentachloride, sodium-chlor, methoxyacetyl chloride or the phosphoryl chloride etc., preferred phosphoryl chloride;
Described phase-transfer catalyst is a kind of in various quaternary ammonium salts, hexadecyl pyridinium bromide salt, cetyl trimethylammonium bromide or the tri-n-octyl methyl ammonium chloride etc., preferred tri-n-octyl methyl ammonium chloride;
Reaction process used between the mol ratio of phenylene dimethyl ether, muriate, Paraformaldehyde 96 and phase-transfer catalyst, promptly between phenylene dimethyl ether: muriate: Paraformaldehyde 96: phase-transfer catalyst is 1:1～4:1～3:0.05～0.3, is preferably 1:2.5:1.3:0.14;
(2), 2,4-dimethoxybenzylamine synthetic
With obtaining 2 in the step (1), 4-dimethoxy benzyl chlorine and Soiodin, urotropine add in the solvent orange 2 A, the stirring reaction Synthetic 2; The 4-dimethoxybenzylamine, the reaction process controlled temperature is 20～60 ℃, is preferably 20～40 ℃; Time is 6h; Finally obtain 2, the 4-dimethoxybenzylamine, its synthetic reaction process synoptic diagram is as shown in Figure 5;
Wherein, described solvent orange 2 A is in acetone, methyl alcohol, ethanol, methylene dichloride or the THF
One or more mixtures, preferred alcohol;
Reaction process used 2, the mol ratio of 4-dimethoxy benzyl chlorine, Soiodin and urotropine, promptly 2,4-dimethoxy benzyl chlorine: Soiodin: urotropine is 1:1～3:1～3, is preferably 1:1:1.
Beneficial effect of the present invention
Of the present invention 2, the compound method of 4-dimethoxybenzylamine be adopt between the industrial goods of wide material sources phenylene dimethyl ether as main raw material through the two-step reaction Synthetic 2, the 4-dimethoxybenzylamine.The first step, a phenylene dimethyl ether in the presence of the quaternary salt of catalytic amount, are reacted synthetic intermediate 2 under the reaction conditions of gentleness in two-phase system, 4-dimethoxy benzyl chlorine, and the selectivity of feed stock conversion and monochloro methylate is all very high.Second step, 2,4-dimethoxy benzyl chlorine and urotropine carry out amination reaction, can quantitative conversion become title product 2, the 4-dimethoxybenzylamine, yield is high, and reaction conditions is gentle.And the used raw material of the present invention all is large industrial goods, and wide material sources are cheap and easy to get, so production cost is lower, again because reaction conditions is gentle, so simple and safe operation.
In addition, compound method of the present invention, final 2, the total yield of 4-dimethoxybenzylamine is 78%, therefore have the advantage that the reaction yield is high, production cost is low, reaction conditions is gentle, and the three wastes that produce is few, is fit to suitability for industrialized production.
Description of drawings
Fig. 1,2, the general structure synoptic diagram of 4-dimethoxybenzylamine
Fig. 2,2, the synthetic reaction process synoptic diagram of 4-dimethoxybenzylamine
Fig. 3,2, the general structure synoptic diagram of 4-dimethoxy benzyl chlorine
Fig. 4,2, the building-up reactions synoptic diagram of 4-dimethoxy benzyl chlorine
Fig. 5,2,4-dimethoxy benzyl chlorine and Soiodin, urotropine Synthetic 2, the reaction process synoptic diagram of 4-dimethoxybenzylamine.
Embodiment
Pass through embodiment below to further explain of the present invention, but do not limit the present invention.
Embodiment 1
A kind of 2, the compound method of 4-dimethoxybenzylamine, its building-up process comprises the following steps:
(1), 2,4-dimethoxy benzyl chlorine synthetic
Phenylene dimethyl ether between in the 200ml vitriol oil (76%), adding (70g, 0.5mol), tri-n-octyl methyl ammonium chloride (28g, 0.07mol), Paraformaldehyde 96 (20.0g; 0.67mol) and phosphoryl chloride (191g, 1.25mol), mixture stirs 4h at 80 ℃; Reaction finishes to tell organic phase, and water is with hexane extraction (3x200ml), and residuum distills behind the recovery solvent; Product 79.1g (GC>97%), yield 85%; B.p. 81-82 ℃/133.3Pa;
(2), 2,4-dimethoxybenzylamine synthetic
Urotropine (42g, 0.3mol), Soiodin (45g, 0.3mol) with 2,4-dimethoxy benzyl chlorine (55.8g; 0.3mol) add in the 1L ethanol, mixed solution is heated to 40 ℃ of stirring at room reactions 6 hours, reacting liquid filtering, and solid is with cold ethanol/water washing; Add 1L ethanol and 200ml concentrated hydrochloric acid then and refluxed 2 hours, cooling back solid precipitation filters, and solid is soluble in water; Regulate pH=11 with NaOH solution, use extracted with diethyl ether, brine wash, drying; Reclaim solvent, vacuum distilling gets 47g2, and 4-dimethoxybenzylamine product (GC>98%), its yield 92%.
The above content is merely the basic explanation of the present invention under conceiving, and according to any equivalent transformation that technical scheme of the present invention is done, all should belong to protection scope of the present invention.
Claims (6)
1. one kind 2, the compound method of 4-dimethoxybenzylamine is characterized in that its building-up process specifically comprises the following step
Suddenly:
(1), 2,4-dimethoxy benzyl chlorine synthetic
Phenylene dimethyl ether, muriate and Paraformaldehyde 96 between in acidic solution, adding, chloromethylation is carried out in heating under the catalysis of phase-transfer catalyst, and the reaction process controlled temperature is 60～120 ℃, and the time is 4h, Synthetic 2,4-dimethoxy benzyl chlorine;
Wherein, described acid is sulfuric acid, concentrated hydrochloric acid or sulfonic acid;
Described muriate is phosphorus trichloride, phosphorus pentachloride, sodium-chlor, methoxyacetyl chloride or phosphoryl chloride;
Described phase-transfer catalyst is various quaternary ammonium salts, hexadecyl pyridinium bromide salt, cetyl trimethylammonium bromide or tri-n-octyl methyl ammonium chloride;
Reaction process used between the mol ratio of phenylene dimethyl ether, muriate, Paraformaldehyde 96 and phase-transfer catalyst, promptly between phenylene dimethyl ether: muriate: Paraformaldehyde 96: phase-transfer catalyst is 1:1～10:1～10:0.01～0.5;
(2), 2,4-dimethoxybenzylamine synthetic
With obtaining 2 in the step (1), 4-dimethoxy benzyl chlorine and Soiodin, urotropine add in the solvent orange 2 A, the stirring reaction Synthetic 2, and 4-dimethoxybenzylamine, reaction process controlled temperature are 20～60 ℃, the time is 6h;
Wherein, described solvent orange 2 A is in acetone, methyl alcohol, ethanol, methylene dichloride or the THF
One or more mixtures;
Reaction process used 2, the mol ratio of 4-dimethoxy benzyl chlorine, Soiodin and urotropine, promptly 2,4-dimethoxy benzyl chlorine: Soiodin: urotropine is 1:1～5:1～5.
2. as claimed in claim 1 a kind of 2, the compound method of 4-dimethoxybenzylamine is characterized in that the synthetic step
Suddenly in (1) reaction process used between the mol ratio of phenylene dimethyl ether, muriate, Paraformaldehyde 96 and phase-transfer catalyst, promptly between phenylene dimethyl ether: muriate: Paraformaldehyde 96: phase-transfer catalyst is preferably 1:1～4:1～3:0.05～0.3;
Described reaction process controlled temperature is preferably 60～80 ℃.
3. according to claim 1 or claim 2 a kind of 2, the compound method of 4-dimethoxybenzylamine is characterized in that closing
Become reaction process in the step (1) used between phenylene dimethyl ether, muriate, Paraformaldehyde 96 and phase transition urge
Change the mol ratio of agent, promptly between phenylene dimethyl ether: muriate: Paraformaldehyde 96: phase-transfer catalyst does
1:2.5:1.3:0.14。
4. as claimed in claim 3 a kind of 2, the compound method of 4-dimethoxybenzylamine is characterized in that the synthetic step
Suddenly in (2) reaction process used 2, the mol ratio of 4-dimethoxy benzyl chlorine, Soiodin and urotropine,
Promptly 2,4-dimethoxy benzyl chlorine: Soiodin: urotropine is preferably 1:1～3:1～3; Described reaction process controlled temperature is preferably 20～40 ℃.
5. as claimed in claim 4 a kind of 2, the compound method of 4-dimethoxybenzylamine is characterized in that the synthetic step
Suddenly in (2) reaction process used 2, the mol ratio of 4-dimethoxy benzyl chlorine, Soiodin and urotropine, promptly 2,4-dimethoxy benzyl chlorine: Soiodin: urotropine is 1:1:1.
6. as claimed in claim 5 a kind of 2, the compound method of 4-dimethoxybenzylamine is characterized in that the synthetic step
Suddenly the reaction process controlled temperature described in (1) is preferably 80 ℃;
Reaction process controlled temperature described in the step (2) is preferably 40 ℃.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105017026A (en) * | 2015-07-02 | 2015-11-04 | 南京杰运医药科技有限公司 | Synthetic method of 2,4-difluorobenzene methylamine |
| CN107286168A (en) * | 2016-03-30 | 2017-10-24 | 山东诚创医药技术开发有限公司 | A kind of N-（3,4- dichloro benzyls）The preparation method of the ammonium of hexa-methylene chlorination four |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4507499A (en) * | 1982-08-31 | 1985-03-26 | Francis S.P.A. | N-(4-Hydroxybenzyl)-3,4,5-trimethoxybenzamide and method for producing trimethobenzamide chlorohydrate |
| CN1749232A (en) * | 2005-09-29 | 2006-03-22 | 上海康鹏化学有限公司 | Process for preparing 2,4,5-triflorophenylacetic acid |
| CN101704755A (en) * | 2009-11-18 | 2010-05-12 | 华中农业大学 | Method for preparing p-tert-butylbenzylamine |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4507499A (en) * | 1982-08-31 | 1985-03-26 | Francis S.P.A. | N-(4-Hydroxybenzyl)-3,4,5-trimethoxybenzamide and method for producing trimethobenzamide chlorohydrate |
| CN1749232A (en) * | 2005-09-29 | 2006-03-22 | 上海康鹏化学有限公司 | Process for preparing 2,4,5-triflorophenylacetic acid |
| CN101704755A (en) * | 2009-11-18 | 2010-05-12 | 华中农业大学 | Method for preparing p-tert-butylbenzylamine |
Non-Patent Citations (1)
| Title |
|---|
| 徐昌盛等: "洛美利嗪的合成", 《中国药科大学学报》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105017026A (en) * | 2015-07-02 | 2015-11-04 | 南京杰运医药科技有限公司 | Synthetic method of 2,4-difluorobenzene methylamine |
| CN107286168A (en) * | 2016-03-30 | 2017-10-24 | 山东诚创医药技术开发有限公司 | A kind of N-（3,4- dichloro benzyls）The preparation method of the ammonium of hexa-methylene chlorination four |
| CN107286168B (en) * | 2016-03-30 | 2019-08-09 | 山东诚创医药技术开发有限公司 | A kind of preparation method of four ammonium of N- (3,4- dichloro benzyl) hexa-methylene chlorination |
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