CN1376660A - Synthesis of substituted trans-cinnamic aldehyde-natural yellow dyestuff from phenylpropyl alkyl derivatives - Google Patents

Abstract

The present invention relates to a method for synthesizing substituted trans-cinnamaldehyde, a natural yellow dye, from phenylpropane derivatives having R ₂ -R ₃ -R ₄ -R ₅ -R ₆ substituents, wherein R ₂ -R ₆ Can be the same or different, can be hydrogen, or hydroxyl, or acyl, or halogen, or alkyl, or heterocyclic, or aryl, or dioxymethylene, or alkoxy, etc. A certain amount of inorganic/organic acid or solid carrier, under microwave radiation, oxidize the above-mentioned phenylpropane derivatives to obtain substituted trans-cinnamaldehyde-natural yellow dye, and the yield is higher than 68-82%; wherein the oxidizing agent can be 2 ,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), p-chloranil, pyridinium chlorochromate (PPC), tert-butyl peroxide or chromium trioxide; solid support Examples include alumina, diatomaceous earth, and silica gel.

Description

Method from the synthetic anti--phenylacrolein-natural yellow dyestuff that replaces of phenylpropyl alkyl derivatives

The present invention relates to " from the method for the synthetic anti--phenylacrolein-natural yellow dyestuff that replaces of phenylpropyl alkyl derivatives ", wherein instead-phenylacrolein (for example, 2,4,5-trimethoxy phenylacrolein, wherein R ₁Be-CH=CH-CHO R ₂=R ₄=R ₅Be-OMe, and R ₃=R ₆Be H; P-met hoxycinnamic aldehyde, wherein R ₁Be-CH=CH-CHO R ₂=R ₃=R ₅=R ₆Be H and R ₄Be-OMe; With 3,4-dimethoxy phenylacrolein, wherein R ₁Be-CH=CH-CHO R ₂=R ₅=R ₆Be H and R ₃=R ₄Be-OMe etc.) molecular formula I as follows:

These compounds can pass through (R ₂-R ₃-R ₄-R ₅-R ₆) phenylpropyl alkyl derivatives (R wherein ₂To R ₆Can be identical or different, be hydrogen or hydroxyl or alkyl or methylene-dioxy or alkoxyl group etc.) oxidation and obtain, in fact these derivatives are natural phenyl propylene (methyl chavicols of wide material sources, methyl allylphenol, oxymethoxyallylbenzene, methyl isoeugenol, safrol, deleterious β-propenyl-2,4,5-trimethoxy beozene etc.) reduzate of bearing essential oil or analogue.

Phenylacrolein and its substitutive derivative are (for example, p-met hoxycinnamic aldehyde, 3,4-methylene-dioxy phenylacrolein, coniferyl aldehyde etc.) contain an aromatic nucleus, have one or more hydroxyls or groups such as dioxy methylene radical or alkoxyl group on the ring, and and α, beta-unsaturated aldehyde (as CH=CH-CHO) links to each other, and the taste of many F﹠B and fragrance are mainly derived from unsaturated aldehyde (Harborne, J.B. and Baxter, H., the vegetable chemistry dictionary, bioactive compounds handbook in the plant, Taylor ﹠amp; Francis Ltd., London WC1N 2ET, 472-488 (1993)).In addition, cinnamylaldehyde derivatives is as the raw material of synthetic multiple other aromatic series spices.And the selective reduction of aldehyde radical obtains styryl carbinol, and it has pleasant and long lasting fragrance, and the reduction fully of side chain obtains phenylpropyl alcohol and oxidation obtains styracin (Muller, A.J., Bowers Jr, J.S., Eubanks, J.R., Geiger, C.C. and Santobianco, J.G., USP 5,939, and 581).Styracin and its ester are useful to flavor compositions.The derivative of phenylacrolein and it can not only prevent skin darkening (Tomoshi, K. and Makoto, the F. that the irradiation because of the sunlight middle-ultraviolet lamp causes effectively, Japanese Patent, No.58055414A2), can also obviously suppress trichomadesis, and promote hair growth (Watanabe, T., Komeno, T. and Hatanaka, M., Japanese Patent, No.6312916A2).In addition, phenylacrolein and fertilizer can be controlled harmful microorganism in the soil together, and to the microorganism of the fertilizer of degrading do not have adverse influence (Saotome, K., Japanese Patent, No.58201703A2).In addition, cinnamylaldehyde derivatives can be used as multiple medicine synthetic intermediate, as antiviral, and AIDS proteinase inhibitor (Castelijns, A.M.C.F., Hogeweg, J.M. and van Nispen, S.P.J.M., USP 5,811,588) especially.Cinnamylaldehyde derivatives also can be used for makeup, dyestuff, agrochemicals, alkaloid (Parmar, V.S., Jain, S.C., Bisht, K.S., Jain, R., Taneja, P., Jha, A., Tyagi, O.D., Prasad, A.K., Wengel, J., Olsen, C.E. and Boll, 597-673 (1997)) and perfume etc. P.M., vegetable chemistry (Phytochemistry), 46 (4):.

(Ceylon cinnamon, plant: found phenylacrolein for the first time in steam distillation method bay section genus), this remains one of main source of phenylacrolein to bark at Ceylon cinnamon in 1833 now.Phenylacrolein also is present in many flowers and the essential oil, as the Hyacinthus class, and Narcissus class, Lavandula class, Wrinkled Gianthyssop Herb and bdellium class and other.But the phenylacrolein (coniferyl aldehyde, coniferyl aldehyde, anisyl aldehyde and hadromal) that replaces is present in other some plants, belongs to class as oak, Acer saccharinun, and the fragrant and sweet flavor that it has the phenols aromaticity is widely used in seasoning composition.Similarly, sinapyladehyde (3,5-dimethoxy-4 '-hydroxyl phenylacrolein) is present in black walnut, and among the Senraincana, and p-met hoxycinnamic aldehyde is present in Rhizome of Grass leaf Sweelflag etc.Usually the phenylacrolein that replaces is an xanchromatic, thereby the application of phenylacrolein can expand the field of natural dyestuff to.But limited amount replacement phenylacrolein can not satisfy worldwide demand in the plant category.Therefore, Jue Daduoshuo phenylacrolein is a synthetic.

Many methods provide the method for synthetic phenylacrolein and its derivative (as p-met hoxycinnamic aldehyde, dimethoxy phenylacrolein, sinapyladehyde, trimethoxy phenylacrolein, methylene-dioxy phenylacrolein etc.).Wherein most methods comprise the phenyl aldehyde (as aubepine etc.) of replacement and acetaldehyde acid or preferably alkali in the presence of react.Phenylacrolein can also synthesize by the hydrolysis of cinnamylidene chlorine.The rosenmund reduction that carries out cinnamyl chloride with palladium catalyst has very high yield (March, J., Advanced Organic Chemistry, reaction, mechanism and structure, Wiley Eastern Ltd., NewDelhi, 396-397, (1987)).Styryl carbinol catalytic dehydrogenation under the high temperature reduced pressure obtains phenylacrolein, and yield is very high.The calcium salt of styracin and formic acid carries out destructive distillation also can obtain aldehyde.In the presence of acid, the yield that the isomery of phenylacetylene base methyl alcohol obtains phenylacrolein is very high.Produce serial α, the practical approach of beta-unsaturated aldehyde is to handle alkene (Brown, H.C. and Tsukamoto with carbon monoxide under the high pressure in the presence of catalyzer, A., J.Am.Chem.Soc., 86:1089 (1964) and Bedoukian, P.Z., spices and seasonings are synthetic, Allured Publishing Corporation, Wheaton, IL, USA, 98-105 (1986)).Although these methods are proved to be effectively, also there are one or more method defectives.For example, require temperature to be lower than ambient temperature in the certain methods of this type, therefore require appreciable method control, in other examples, reaction can only be carried out under high relatively pressure, and forms reaction mixture.

The reference of typical prior art comprises USP 2,529,186; 2,794,813; 3,028,419 and German Patent No.97,620; 1,114,798 and russian patent No.1451139A1 and Czech patents No.8405411A1.

Therefore, the purpose of this invention is to provide a kind of method of producing phenylacrolein, for example, p-met hoxycinnamic aldehyde, 3,4-dimethoxy phenylacrolein, 3,4-methylene-dioxy phenylacrolein, 3,4-methylene-dioxy-5-methoxycinnamic aldehyde, 1-oxyethyl group-2-acetoxyl group phenylacrolein, 1-oxyethyl group-2-hydroxyl phenylacrolein, sinapyladehyde, 2,5-dimethoxy-3,4-methylene-dioxy phenylacrolein, 2-methoxyl group-4,5-methylene-dioxy phenylacrolein, coniferyl aldehyde, 3,4,5-trimethoxy phenylacrolein, 2, the 3-dimethoxy-4 ', 5-methylene-dioxy phenylacrolein and 2,4,5-trimethoxy phenylacrolein etc., this method can be eliminated shortcoming discussed above.

Other purpose of the present invention below is described.

Main purpose of the present invention is to develop a simple commercial run, its from phenylpropyl alkyl derivatives (as dihydro methyl chavicol, dihydro methyleugenol, 2,4,5-trimethoxy-benzene propane etc.) one-step synthesis replaces phenylacrolein (p-met hoxycinnamic aldehyde, 3,4-dimethoxy phenylacrolein, 2,4,5-trimethoxy phenylacrolein etc.), and yield is higher.In fact, phenylpropyl alkyl derivatives is the hydrogenation products of the natural phenyl propylene (for example, methyl chavicol or methyl allylphenol, methyleugenol, highly toxic β-propenyl-2,4,5-trimethoxy beozene) of wide material sources.

Another object of the present invention is to develop a simple method, its synthetic replaces the purity height of phenylacrolein, and is not polluted by corresponding cinnamic acid and alcohol.

Another object of the present invention also is to develop a simple method, its be exclusively used in a step from phenylpropyl alkyl derivatives synthetic anti--phenylacrolein.

Another object of the present invention also is to develop a simple method, and it is used for the synthetic on a large scale phenylacrolein-natural yellow dyestuff that replaces.These phenylacroleins have multiple use, as the painted and seasoning of food be used for medicine industry etc.

Another object of the present invention also is to develop a simple and method fast, its under microwave radiation in several seconds to the blink of several minutes the synthetic phenylacrolein that replaces.

Another object of the present invention also is to develop a method of using the synthetic phenylacrolein that replaces of dihydro product of simple and inexpensive, these dihydro product origin source natural widely phenyl propylene bearing oils such as chavicol, methyl allylphenol.Oxymethoxyallylbenzenes etc. obtain.

Another object of the present invention also is to use the synthetic replacement of other deleterious essential oil phenylacrolein, and improves its use value.These deleterious essential oils comprise the similar poisonous oil of safrol or β-propenyl-2,4,5-trimethoxy beozene or other.

Another object of the present invention also is to provide first a Synthetic 2,4, the method of 5-trimethoxy phenylacrolein or analogue, these compounds can and be used for synthesizing heterocyclic and other purposes that bioactive compound is arranged as the simple initial substance that synthesizes corresponding cinnamic acid, ester, amide derivatives.

Thereby, the invention provides a kind of use 2,3-two chloro-5,6-dicyano-1,4-benzoquinones (DDQ) in the presence of catalyzer, synthesize the method for the anti--phenylacrolein that replaces as effective oxidising agent, and catalyzer refers to acetate, tosic acid, silica gel.

Thereby, the invention provides a kind of from corresponding (R ₂-R ₃-R ₄-R ₅-R ₆) method of the synthetic anti--phenylacrolein-natural yellow dyestuff that replaces of phenylpropyl alkyl derivatives, anti--phenylacrolein has the structural formula I##STR## shown in the accompanying drawing 4, wherein R ₁Be fixed as-CH=CH-CHO R ₂, R ₃, R ₄, R ₅, R ₆Be independently selected from i respectively) hydrogen atom; Ii) alkoxyl group but R ₂, R ₃, R ₄, R ₅, R ₆In at least two be hydrogen atom or alkoxyl group but methylene-dioxy and hydroxyl, alkoxyl group, alkyl, aryl or hydrogen atom combination with 1-12 carbon atom, or an alkoxyl group but a hydroxyl make up with methylene-dioxy, hydroxyl, alkoxyl group, the alkyl with 1-12 carbon atom, aryl or hydrogen atom; Iii) methylene-dioxy and R ₂, R ₃, R ₄, R ₅, R ₆In at least three be alkoxyl group, hydroxyl, have an arbitrary combination of alkyl, aryl or the hydrogen atom of 1-12 carbon atom; Vi) hydroxyl but R ₂, R ₃, R ₄, R ₅, R ₆In at least one is the arbitrary combination vii) protected hydroxyl such as the ethanoyl of hydrogen atom and alkoxyl group, hydroxyl, methylene-dioxy, the alkyl with 1-12 carbon atom, aryl or hydrogen atom, benzyl, but R ₂, R ₃, R ₄, R ₅, R ₆In at least one is the arbitrary combination of hydrogen atom and alkoxyl group, hydroxyl, methylene-dioxy, the alkyl with 1-12 carbon atom, aryl or hydrogen atom.Aforesaid method is included under the existence of solvent and catalyzer, use oxygenant with respect to the mol ratio of phenylpropyl alkyl derivatives between 1: 1 to 1: 8, temperature of reaction is between-15 ℃ to 210 ℃, phenylpropyl alkyl derivatives with oxidation in 30 minutes to 48 hours replacement, removal of solvent under reduced pressure, and obtaining having anti--phenylacrolein of structural formula I with the usual manner separated product, yield is between 68-82%.

It should be noted that, find that first above-mentioned can effective cost-effective method be to help in the Oxybenzene propane method two independent steps (in other words at DDQ, dehydrogenation and oxidation) afterclap, wherein phenylpropyl alcohol alkane is actually natural phenyl propylene (the methyl chavicol for example of wide material sources, oxymethoxyallylbenzene, the dimethyl isoeugenol), comprise that some are deleterious and have a mind to the phenyl acryloyl derivative of forbidding such as the reduzate of safrol and β-propenyl-2,4,5-trimethoxy beozene.

In a specific embodiment of the present invention, the solvent of use is selected from ether, tetrahydrofuran (THF), glycol dimethyl ether ， diox, phenyl ether, chlorinated solvent such as methylene dichloride, chloroform and orthodichlorobenzene, aromatic hydrocarbons such as benzene,toluene,xylene and organic acid such as formic acid, acetate.

In another embodiment of the present invention, the oxygenant of use is selected from 2,3-two chloro-5, and 6-dicyano-1,4-benzoquinones (DDQ), to chloranil, pyridinium chloro-chromate (PPC), tert-butyl peroxide, chromium trioxide and corresponding mixture.

Of the present invention also have in the embodiment, the oxygenant of use with respect to the mol ratio of reactant between 1: 1.5 to 1: 5.

In another embodiment of the present invention, temperature of reaction is between 30-140 ℃.

In another embodiment of the present invention, the reaction times is between 4-16 hour.

In another embodiment of the present invention, the catalyzer that uses is selected from hydrochloric acid, sulfuric acid, Cu (I) or Fe (III) salt, Periodic acid, organic acid such as acetate, propionic acid, butyric acid, ion exchange resin such as IR-120H and sulfonated polystyrene resin, tosic acid (PTSA) and macroporous resin such as macroporous resin 15.

In another embodiment of the present invention, the initial substance phenylpropyl alcohol alkane of use can obtain after the natural allyl group that the three kinds of isomer are arranged/phenyl acryloyl derivative reduction of allyl benzene and phenylallene derivative or wide material sources.

In another embodiment of the present invention, Oxybenzene propane obtains instead-phenylacrolein, and it is similar to the isomer that obtains from plant.

In another embodiment of the present invention, deleterious β-(cis) and γ-isomer can change into the higher natural dyestuff of added value.

In another embodiment of the present invention, the β-propenyl-2,4,5-trimethoxy beozene of having a mind to forbid that obtains from Rhizome of Grass leaf Sweelflag can change into useful natural yellow dyestuff.

In another embodiment of the present invention, described method can be used for the scale operation cinnamylaldehyde derivatives.

In another embodiment of the present invention, aforesaid method provides some novel cinnamylaldehyde derivatives, can be used as natural tinting material, oxidation inhibitor and antiseptic-germicide.

In another embodiment of the present invention, aforesaid method provides DDQH ₂(by product) between the yield 91-94%, and then generates DDQ, reduced the cost of synthetic cinnamylaldehyde derivatives.

In another embodiment of the present invention, the phenyl alkanes that aforesaid method can oxidation has 2n-1 carbon atom becomes corresponding unsaturated aldehyde, wherein n 2-6 or more between change.

In another embodiment of the present invention, above-mentioned phenylpropyl alcohol alkane can stand multiple reaction, for example halogenation, dehydrogenation, allyl group halogenation, formylation, list and/or dicarbapentaboraneization, condensation reaction.

In another embodiment of the present invention, the phenylacrolein that aforesaid method provides is not polluted by corresponding acid and alcohol.

In another embodiment of the present invention, some phenylacroleins are as 2,4, and the yield of 5-trimethoxy phenylacrolein is higher, and can be used as the simple initial substance of synthetic corresponding multiple novel unsaturated acid, ester, acid amides and alcohol derivate.

In another embodiment of the present invention, some phenylacroleins are as 2,4, and the yield of 5-trimethoxy phenylacrolein is higher, and can be used as the simple initial substance of synthetic corresponding multiple novel dihydro (saturated) acid, ester, acid amides and alcohol derivate.

In another embodiment of the present invention, the product that obtains has i) 2,4,5-trimethoxy phenylacrolein, wherein R ₁Be-CH=CH-CHO R ₂=R ₄=R ₅Be-OMe R ₃=R ₆Be H; Ii) p-met hoxycinnamic aldehyde, wherein R ₁Be-CH=CH-CHO R ₂=R ₃=R ₅=R ₆Be H and R ₄Be-OMe; Iii) 3,4-dimethoxy phenylacrolein, wherein R ₁Be-CH=CH-CHO R ₂=R ₅=R ₆Be H and R ₃=R ₄Be-OMe.

Another embodiment of the present invention provides the method for the anti--phenylacrolein-natural yellow dyestuff that synthesizes the replacement with structural formula I, aforesaid method is included under the existence of solvent and catalyzer, use oxygenant and solid carrier, the mol ratio of oxygenant is between 1-20, use the microwave radiation of 600 watts of mid power, with the phenylpropyl alkyl derivatives that 20 seconds to 12 minutes time oxidations replace, removal of solvent under reduced pressure, and with the usual manner separated product obtain having structural formula I instead-phenylacrolein.

In the another embodiment of the present invention, solid carrier is selected from diatomite, silica gel, molecular sieve and aluminum oxide.

In the another embodiment of the present invention, the product that obtains by microwave radiation means is i) 2,4,5-trimethoxy phenylacrolein, wherein R ₁Be-CH=CH-CHO R ₂=R ₄=R ₅Be-OMe R ₃=R ₆Be H; Ii) p-met hoxycinnamic aldehyde, wherein R ₁Be-CH=CH-CHO R ₂=R ₃=R ₅=R ₆Be H and R ₄Be-OMe; Iii) 3,4-dimethoxy phenylacrolein, wherein R ₁Be-CH=CH-CHO R ₂=R ₅=R ₆Be H and R ₃=R ₄Be-OMe.

In brief, the invention provides a kind of from corresponding (R ₂-R ₃-R ₄-R ₅-R ₆) phenylpropyl alkyl derivatives (for example, dihydroanethole, wherein R ₂=R ₃=R ₅=R ₆Be H and R ₄Be-OMe; Dihydro methyleugenol, wherein R ₂=R ₅=R ₆Be H and R ₃=R ₄Be-OMe; With dihydro propenyl-2,4,5-trimethoxy beozene, wherein R ₂=R ₄=R ₅Be-OMe R ₃=R ₆Be H etc.) synthetic replace anti--phenylacrolein, natural yellow dyestuff, method, R wherein ₁Be fixed as-CH=CH-CHO R ₂, R ₃, R ₄, R ₅, R ₆Be i independently respectively) hydrogen atom; Ii) alkoxyl group but R ₂, R ₃, R ₄, R ₅, R ₆In at least two be hydrogen atom or alkoxyl group but methylene-dioxy and hydroxyl, alkoxyl group, alkyl, aryl or hydrogen atom arbitrary combination with 1-12 carbon atom, or alkoxyl group but hydroxyl and methylene-dioxy, alkoxyl group, the alkyl with 1-12 carbon atom, aryl or hydrogen atom make up arbitrarily; Iii) methylene-dioxy and R ₂, R ₃, R ₄, R ₅, R ₆In at least three be alkoxyl group, hydroxyl, have alkyl, aryl or a hydrogen atom arbitrary combination of 1-12 carbon atom; Iv) hydroxyl but R ₂, R ₃, R ₄, R ₅, R ₆In at least one is hydrogen atom and arbitrary combination such as alkoxyl group, hydroxyl, methylene-dioxy, the alkyl with 1-12 carbon atom, aryl or hydrogen atom; V) protected hydroxyl such as ethanoyl, benzyl etc. but R ₂, R ₃, R ₄, R ₅, R ₆In at least one is hydrogen atom and arbitrary combination such as alkoxyl group, hydroxyl, methylene-dioxy, the alkyl with 1-12 carbon atom, aryl or hydrogen atom.Aforesaid method comprises that step (a) provides the phenylpropyl alcohol that is dissolved in following solvent alkane, such as but not limited to 2,4,5-trimethoxy-benzene propane (dihydro propenyl-2,4,5-trimethoxy beozene), solvent has, as ether, such as but not limited to ether, tetrahydrofuran (THF), glycol dimethyl ether, diox and phenyl ether etc.; Chlorinated solvent is such as but not limited to methylene dichloride, chloroform and orthodichlorobenzene; Aromatic hydrocarbons as but be not limited to benzene,toluene,xylene; And organic acid, such as but not limited to formic acid, acetate etc.; (b) Oxybenzene propane derivative in the presence of oxygenant, oxygenant be such as but not limited to 2,3-two chloro-5,6-dicyano-1,4-benzoquinones (DDQ), or to chloranil, or pyridinium chloro-chromate (PPC), or tert-butyl peroxide, or chromium trioxide, or corresponding mixture, the ratio of use is at 1-20 times of mole, and preferred 1.5-8 is mole doubly, temperature of reaction is between-15 ℃ to+210 ℃, preferably between 30 ℃ to 140 ℃, the reaction times is between 30 minutes to 48 hours, between preferred 4-16 hour; (c) in the presence of catalyzer, under microwave radiation, in 20 seconds to 12 minutes very short time, it is very smooth that oxidation step carries out ground, and yield is higher, and catalyzer mainly is a mineral acid, such as but not limited to hydrochloric acid, sulfuric acid, perhaps Cu (I) or Fe (III) salt, or Periodic acid, or organic acid, such as but not limited to acetate, propionic acid, butyric acid, ion exchange resin such as IR-120H, the sulfonated polystyrene resin, tosic acid (PTSA) and macroporous resin such as macroporous resin 15 perhaps contain the solid carrier of the solution of phenylpropyl alcohol alkane and oxidising agent more than the absorption, solid carrier is such as but not limited to diatomite, silica gel, molecular sieve and aluminum oxide etc.; (d) mixture filters, and the pressure reducing and steaming solvent, and product separates with conventional mode, in other words, and extraction, distillation, recrystallization and chromatography, product (as, 2,4 of said structure formula I, 5-trimethoxy phenylacrolein, wherein R ₁Be-CH=CH-CHO R ₂=R ₄=R ₅Be-OMe R ₃=R ₆Be H; With 3,4-dimethoxy phenylacrolein, wherein R ₁Be-CH=CH-CHO R ₂=R ₅=R ₆Be H and R ₃=R ₄Be-OMe) yield preferably makees oxygenant with benzoquinones between 68-82%, and yield is higher.

In the another embodiment of the present invention, a simple method that is used to obtain replacing anti--phenylacrolein is described.In fact, the phenylpropyl alcohol alkane from the source simple and inexpensive that obtains of natural widely phenyl propylene hydrogenation can be used for the synthetic very high cinnamylaldehyde derivatives that is worth as initial substance.

In the another embodiment of the present invention, describe one and be used for the synthetic simple one step process that replaces phenylacrolein, yield and product purity are all very high, do not have the pollution of respective acids and alcohol.

In the another embodiment of the present invention, replace phenylacrolein and can be used as food, the natural yellow dyestuff of the painted usefulness in weaving and the pharmaceutical prod.

Another embodiment of the present invention is a simple method, can be used for scale operation.

Class phenylpropyl alcohol hydride compounds (C6-C3) comprises the phenyl propylene, phenyl-acetone, and phenylacrolein, styryl carbinol, the derivative of styracin and ester is found these compound biologically actives, and is had commercial value.In these class phenylpropyl alcohol hydride compounds, (R ₂-R ₃-R ₄-R ₅-R ₆) cinnamylaldehyde derivatives often is present in the essential oil, R wherein ₂To R ₆Can be identical or different, can be hydrogen, or hydroxyl, or methylene-dioxy, or alkoxyl group etc.Use as each and to be paid close attention to, these phenylacroleins can be widely used in spices, seasonings, and makeup, alcoholic beverage and medical supplies etc. also can be used for the pheromone of insect, antiseptic-germicide, anti-mycotic agent etc.Phenylacrolein is in the widespread use (F.E.M.A.no.2286) of spices in the pharmaceutical preparation, and can be used as the intermediate of synthetic biologically active compound, and such importance has attracted many chemists' attention (Muller, A.J., Bowers, Jr, J.S., Eubanks, J.R., Geiger, C.C., and Santobianco, J.G., USP5,939,581 and Castelijns, A.M.C.F., Hogeweg, J.M. and Van Nispen, S.P.J.M., USP 5,811, and 588).The main source of phenylacrolein (synonym: phenylacrolein, 3-phenylacrolein or cinnamylidene or γ-phenylacrolein or cinnamic aldehyde) is a Chinese cassia tree (Ceylon cinnamon, bay section belongs to) bark, and the content of the contained cinnamyl acetate of fresh bark is higher, and cinnamyl acetate can discharge phenylacrolein by the participation of enzymatic hydrolysis and reversible aldehyde-pure oxydo-reductase in the fermentation process of scale operation.In addition, the cinnamomic leaf also contains a large amount of oxymethoxyallylbenzenes and very small amount of phenylacrolein.Similarly, another source of phenylacrolein is the Cinnamomum Chinese cassia tree, it is widely used in conventional Chinese medicine (Tang, W., and Eisenbrand, G.: the Chinese medicine that derives from plant, Springer-Verlag, New York, pp.319-330 (1992)) as pain relieving, be good for the stomach and the reagent of anti-inflammatory, find that its activity depends primarily on high-load phenylacrolein (85%).In addition, phenylacrolein has the antimutagenic activity of chemical mutagen or uv-radiation (Kakimuma, K., Koike, J., Kotanik, K., Ikekawa, W., Kado, T. and Nomoto, M., Agric.Biol.Chem.48:1905-1906 (1984); Ohta, T., Watanabe, K., Moriya, M., Shirasu, Y., Kada, T., Mutat.Res., 107:219-227 (1983)).Concentration is the growth that the phenylacrolein of 4.8 mcg/ml can suppress in the culture 50% L1210 leukemia cell, and finds that aldehyde group works to above-mentioned activity.Phenylacrolein also can suppress in the mouse growth (CA 94:168054K and Moon, K.H., Pack, M.Y., Drug Chem., Toxicol., 6:521-535 (1983)) of the tumour W2K-11 that caused by SV40.

Similarly, the phenylacrolein of some replacements, as o-methoxy cinnamic aldehyde (synonym: adjacent hydroxyl phenylacrolein methyl ether), p-met hoxycinnamic aldehyde (synonym: the p-hydroxycinnamic aldehyde methyl ether), 3,4-dimethoxy phenylacrolein (synonym: single coniferyl aldehyde or methyl hadromal), to coniferyl aldehyde (synonym: hadromal, maple leaf aldehyde or 4-hydroxyl-3-methoxycinnamic aldehyde), 3,4-methylene-dioxy phenylacrolein (synonym: piperonyl propenal, 3,4-methylene-dioxy Ben Yajiaji acetaldehyde, or piperonylidene acetaldehyde), sinapyladehyde (synonym: 2,4-dimethoxy-4 '-hydroxyl phenylacrolein) also be widely used in the seasoning composition, but the smell of the compound of these replacements is only similar slightly on sense organ to the smell of phenylacrolein.In addition, the known biologically active of the phenylacrolein of some replacements.2 '-hydroxyl phenylacrolein can suppress farnesyl-protein transferase (FPTase) (Knon, B.M., Cho, Y.K., Lee, S.H., Nam, J.Y., Bok, S.H., Chun, S.K., Kim, J.A. and Lee, I.R., PlantaMedica, 62:183-184 (1996)), and can be used as active anticancer compound (Lee, C.W., Hong, D.H., Han, S.B., Park, S.H., Kim, H.K., Kwon, B.M. and Kim, H.M., Planta Medica, 65:263-266 (1999)).3 ', 4 '-dimethoxy phenylacrolein reduces the ileum grinding belt of cavy to LTD ₄Systole response.Similarly, the phenylacrolein of replacement is powerful oxidation inhibitor (Kikuzaki, H. as 4-hydroxyl-3-methoxycinnamic aldehyde, Hara, S., Kawai, Y. and Nakatani, N., Phytochemistry, 52,1307-1312 (1999)), discovery can be used as inhibition compound (Kim, N.Y., the Pae that causes oxynitride synthetic (iNOS), H.O., Ko, Y.S., Yoo, J.C., Choi, B.M., Jun, C.D., Chung, H.T., Inagaki, M., Higuchi, R. and Kim, Y.C., Planta Medica, 65:656-658 (1999)).But therefore the phenylacrolein that has only replacement seldom in the plant can only adopt chemosynthesis to obtain.Some important method are:

(a) benzene derivative of Qu Daiing and nitrosodimethylaniline react (CA 51,7326 (1957)) in the presence of mineral acid and catalyzer;

(b) acetal of Vinyl Ether and aromatic aldehyde carries out condensation reaction (Friedrich and Hartmann, Chem.Ber., 94,838 (1961));

(c) Grignard reagent of bromobenzene and 1-(methylphenylamine base) propylene-3-aldehyde reaction (Jutz, Ger.Pat.1,114,798, October 12, (1961));

(d) under pressure, in the presence of catalyzer, suitable alkene and reaction of carbon monoxide (USP 3,028,419, April 3, (1962));

(e) claisen-Schmidt reation of aromatic aldehyde and acetaldehyde obtains phenylacrolein, and yield depends primarily on the aromatic aldehyde of use at 12-30%.The low yield of reaction product may ascribe self condensation (Richmond, USP 2,529,186, November 7, (1950)) of acetaldehyde to;

(f) after the reaction of aromatic aldehyde and phosphoryl triethyl acetate; the reduction reaction of ethyl cinnamate and lithium aluminium hydride (LAH) generates corresponding styryl carbinol; styryl carbinol is oxidized to phenylacrolein (Rajasekhar with Manganse Dioxide then; D. and Subbaraju; G.V.; Indian J.Chem., 38,837-838 (1999)).But this is a multistep method, and needs expensive reagent;

(g) two (triphenylphosphine) tetrahydrochysene boric acid copper reductions (El-Feraly, F.S. and Hoffstetter, M.D., J.Nat.Prod.43,407 (1980)) are used in styracin and thionyl chloride reaction subsequently;

(h) aromatic aldehyde and deleterious potassium cyanide reagent react (Deuchert, S.K., Hertenstein, U. and Hunig, S., Synthesis, 777 (1973)); With

(i) N, N-dimethyl benzamide and hydrogenation diethoxy aluminium lithium reaction (Perum, T.J., Zeftel, L., Nelb, R.G. and Tarbell, D.S., J.Org.Chem., 28,2937 (1963)).

More than all methods multiple restriction is all arranged, for example yield is low, expensive reagent and form undesirable by product.And very strange, although the output of annual phenylacrolein is very high, about its synthetic chemistry and patent documentation but seldom.Because above all problems, we invent a kind of simple commercial run, are used for a step from the synthetic phenylacrolein that replaces of phenylpropyl alcohol alkane.Applicant's knowledge also and does not find to have oxidation phenylpropyl alcohol alkane to generate the report of the cinnamylaldehyde derivatives that replaces extremely to the greatest extent.The reduction of the two keys by phenyl propylene bearing essential oil (as methyl chavicol, methyl allylphenol, oxymethoxyallylbenzene, safrol, β-propenyl-2,4,5-trimethoxy beozene etc.) can obtain simple initial compounds.In addition, phenylpropyl alkyl derivatives can obtain (organic synthesis, the Coll. first roll, 471 pages) by the Grignard reaction of benzyl chloride derivative and ethyl sulfate.But, it should be noted that in exploitation and synthesize in the method method of anti--phenyl propylene (alpha-ararin) that the applicant has invented above from 2 with pharmacologically active, 4, method (Janusz, the P. of the synthetic phenylacrolein that replaces of the reduzate of 5-trimethoxy-benzene propane-a kind of deleterious β-propenyl-2,4,5-trimethoxy beozene, Bozena, L., Alina, T.D., Barbara, L., Stanislaw, W., Danuta, S., Jacek, P., Roman, K., Jacek, C., Malgorzata, S., Zdzislaw, C., J.Med.Chem., 43,3671-3676 (2000)).

The phenyl propylene that is widely used in spices, seasonings, makeup, alcoholic beverage, whisky and medicine industry has three kinds of isomeric forms (α, β and γ in other words), but the cis-isomeride of phenyl propylene (as β-propenyl-2,4,5-trimethoxy beozene) is proved to be carcinogens and poisonous (Taylor, J.M., Jones recently, W.I., Hogan, E.C., Gross, M.A., David, D.A. and Cook, E.L., Toxicol.Appl.Pharmacol., 10:405 (1967); Keller, K., Odenthal, K.P. and Leng, P.E., Planta Medica, 1:6-9 (1985) and Kim, S.C., Liem, A., Stewart, B.C. and Miller, J.A., Carcinogensis, 20 (7), 1303-1307 (1999)), thus its any purposes in seasonings, spices and medicine industry all be under an embargo.The toxicity of finding suitable-methyl allylphenol is 15 times of anti--methyl allylphenol.Similarly, the γ-isomer of phenyl propylene (as safrol) also is found to be carcinogens (Daimon, H., Sawada, S., Asakura, S. and Sagami, F., Carcinogensis, 19 (1): 141-146, (1998) and Liu, T.Y., Chen, C.C., Chen, C.L. and Chi, C.W., food and chemical toxicology (Food ﹠amp; Chemical Toxicology), 37 (7): 697-702, (1999)).Because the problems referred to above, the most affected plant are that (plant: Araeceae), wherein the content of deleterious β-propenyl-2,4,5-trimethoxy beozene depends on the kind (Riaz of Rhizome of Grass leaf Sweelflag to Rhizome of Grass leaf Sweelflag, M., Shadab, Q., Chaudhary, F.M., Hamdard Medicus 38 (2): 50-62 (1995) and McGuffin, M., Hobbs, C., Upton, R. and Goldberg, A., the phytology security manual of U.S. draft product association, CRC Press, Inc.; Boca Raton, Florida:USA, 231, (1997)).The content of the β-propenyl-2,4,5-trimethoxy beozene in the triploid kind is 8-19%, and the content of the middle β-propenyl-2,4,5-trimethoxy beozene of tetraploid and hexaploid kind (extensively existing in Asian countries) is up to 96%.On the contrary, do not find β-propenyl-2,4,5-trimethoxy beozene in the liploid variety.Therefore, the oil of Rhizoma Acori Graminei that obtains from the liploid variety (not having β-propenyl-2,4,5-trimethoxy beozene) and the Eastern Europe triploid kind (up to 12% β-propenyl-2,4,5-trimethoxy beozene) of North America is considered to clinically effectively and safety, and the oil of Rhizoma Acori Graminei that area, Asia (India, Pakistan, Bangladesh, Nepal, Japan and China) obtains is because contained β-propenyl-2,4,5-trimethoxy beozene up to 70-96%, thereby weakened the market potential (Mazza of oil of Rhizoma Acori Graminei, G., J.of Chromatography, 328:179-206 (1985); Nigam, M.C., Ateeque, A., Nisra, L.N. and Ahmad, A., Indian Perfumer 34:282-285 (1990) and Bonaccorsi, I., Cortroneo, A., Chowdhury, J.U. and Yusuf, M., Essenze Derv.Agrum, 67 (4): 392-403 (1997)).Therefore, applicant's purpose is to use deleterious β-propenyl-2,4,5-trimethoxy beozene (suitable-2,4,5-trimethoxyphenyl-1-propylene) to obtain the product of high added value by its reduzate as initial substance, this reduzate (2 of recent findings, 4,5-trimethoxy-benzene propane) be a kind of useful new aromatic molecule, its toxicity is than β-propenyl-2,4,5-trimethoxy beozene or the low at least 6-4 times of (Sinha of oil of Rhizoma Acori Graminei, A.K., USPNo.09, application on August 31st, 652376,2000).In addition, 2,4,5-trimethoxy-benzene propane says it is synthetic anti--2,4 for us, the simple intermediate of 5-trimethoxyphenyl-1-propylene (alpha-ararin).

What is interesting is, when 2,4,5-trimethoxy-benzene propane is with 2,3-two chloro-5,6-dicyano-1,4-benzoquinones (DDQ) is handled and is obtained alpha-ararin (with the contrast of standard alpha-ararin), and very strong yellow spotting and some unreacted initial substances (clearly showing on thin layer chromatography board) are arranged.The consumption that improves DDQ more helps the generation of yellow substance rather than alpha-ararin.All three kinds of products use column chromatography, and wherein yellow solid (140 ℃ of fusing points) shows that infrared absorption peak is at 1648cm ^-1(conjugation carbonyl), and 2, the 4-DNP test is positive, therefore confirms to exist carbonyl.(λ is 244,298 to the maximum to the UV spectrum of yellow solid, 366nm) further confirms with respect to initial substance 2,4, and (λ is 269 to the maximum, and 301nm) conjugacy improves for 5-trimethoxy-benzene propane (λ is 288nm to the maximum) and alpha-ararin.Yellow solid ¹HNMR (Fig. 1) shows 14 protons (referring to example I), wherein two bimodal and two-folds bimodal correspond respectively to three protons chemical shift δ 9.65 (1H, d, J=7.8Hz), 7.81 (1H, d is J=15.8Hz) with δ 6.64 (1H, dd, J=15.8Hz, J=7.8Hz).In addition, on two aromatic rings proton unimodal with three trimethoxies on the unimodal position of nine protons compare more or less identical (Patra, A. and Mitra, A.K., Phytochemistry, 44:668-669 (1981)) with the δ value of β-propenyl-2,4,5-trimethoxy beozene.IR and ¹H NMR confirms that undersaturated aldehyde radical is arranged and (CH=CH-CHO) links to each other with the phenyl ring (two protons) that trimethoxy (nine protons) replaces.Similarly, yellow solid ¹³C NMR (Fig. 2) is respectively in δ 194.1,154.1,153.2,147.6,143.3,126.4,114.5,110.5,96.5,56.4 56.2,56.0 have chemical shift, (existence CH=CH-CHO) and that demonstration may be because the beta-unsaturated aldehyde base except the position of carbon on the side chain propyl group respectively at δ 194.1 (C-3 '), (154.1 C-1 '), 126.4 (C-2 '), the position of 12 carbon and β-propenyl-2,4,5-trimethoxy beozene similar.The EI mass spectrum (Fig. 3) of yellow solid shows one [M] clearly ⁺The peak is 222 places at m/z.Based on above spectroscopic data, infer that yellow solid is 2,4, the trans-isomer(ide) (example I) of 5-trimethoxy phenylacrolein.Form unexpected anti--2,4,5-trimethoxy phenylacrolein confirms by the following method that finally (i) becomes known 2 with neutral potassium permanganate oxidation in ice-cold acetone, 4,5-TMB (example II) (Birch, A.J., Jackson, A.H., Shannon, P.V.R. and Steward, G.W., Journal of Chemical Society Perkin Trans I, 2492-2501 (1973) and Starkovsky, N.A., Journal of Organic Chemistry, 27,3733-3734, (1962)); (ii) use selenium oxide direct oxidation β-propenyl-2,4,5-trimethoxy beozene (Liu M C, Lin T S ﹠amp; Sartorelli A C, JMed Chem, 35,3671 (1992)) generate asarylaldehyde (EXAMPLE III) and compare with the natural phenylacrolein of report.In the Zai diox with behind selenium oxide and several alkaline purification β-propenyl-2,4,5-trimethoxy beozenes as pyridine, triethylamine etc., on thin layer chromatography board, show two spots clearly, wherein the yellow spotting expection is 2,4, the 5-TMB, and speckle is corresponding styryl carbinol derivative, confirms by the absorption peak of IR spectrum at 1648 (carbonyls) and 3480 (hydroxyls).Bring up to 1.3 equivalents when the consumption of selenium oxide and can generate the latter.Several analogues at β-propenyl-2,4,5-trimethoxy beozene carry out can forming by-product alcohol usually when obtaining aldehyde in the method for allyl oxidation with the selenium oxide processing.But observe, do not separate direct mixture (Lin, the S.J. that handles phenylacrolein and alcohol with pyridinium chloro-chromate (PCC), Short, R.E., Ford, S.P., Grings, E.E. and Rasazza, P.N., J.Nat.Prod, 61,51-56, (1998)) have to 2,4, point of 5-trimethoxy phenylacrolein is because the spot of alcohol also is oxidized to phenylacrolein.Phenylacrolein ¹H NMR spectroscopic data similar to the natural product of report (Kulkarni, M.M., Sohani, J., Rojatkar, S.R. and Nagasampagi, B.A., Indian J.Chem., 25B:981-982 (1986)), and here report for the first time ¹³C NMR spectroscopic data.Therefore, the separation of above-mentioned phenylacrolein and sign disclose a variation route from the phenylacrolein of the multiple replacement of phenylpropyl alkyl derivatives one-step synthesis.

After the phenylacrolein of successfully confirming to replace, the applicant mainly pays close attention to the per-cent that improves phenylacrolein (natural dyestuff), because because the security and the environmental friendliness characteristic of natural colorant, the demand to natural product in the world wide constantly improves with respect to synthetics.Therefore, we observe with DDQ processing phenylpropyl alcohol alkane in 1-20 molar range (preferred 1.5-8 mole) and mainly obtain phenylacrolein.Form unsaturated aldehyde from saturated propane side chain and may mainly single step, form the phenyl propylene, reoxidize the formation phenylacrolein by elder generation.By using catalyzer, as mineral acid (hydrochloric acid, sulfuric acid), perhaps copper (I) or iron (II) salt, or Periodic acid, or organic acid such as acetate, propionic acid, butyric acid, ion exchange resin such as IR-120H, sulfonated polystyrene resin, tosic acid (PTSA) etc. can further improve the yield of phenylacrolein.Absorption contains 1-propyl group-2 on following solid carrier, 4, the solution of 5-trimethoxy-benzene and oxygenant DDQ can form phenylacrolein in very short time under microwave radiation, solid carrier is meant diatomite, silica gel, molecular sieve and aluminum oxide (Posner, G.H. and Rogers, D.Z., J.Am.Chem.Soc.99,8208 (1997); Jr.Filippo, J.S. and Chern, C.I., J.Org.Chem.42,2182 (1979)) (EXAMPLE IV), the reaction times is between 40 seconds to 20 minutes, between preferred 2-12 minute.It should be noted that at some oxygenants (as Manganse Dioxide, or to chloranil, or pyridinium chloro-chromate, or tert-butyl peroxide, chromium trioxide) in, find that DDQ is the strongest dehydrogenation reagent (Sondengam, B.L. and Kimbu, S.F., Tetrahedron Letters, 1:69-70, (19977) and Guy, A., Lemaire, M., and Guette, J.P., Chem.Commun.8 (1980)) and oxidising agent (Berker, H.D., J.Org.Chem.30,982 (1965)), it can make one step of phenylpropyl alkyl derivatives change into trans-isomer(ide) (Lemaire, M., the Guy of corresponding phenylacrolein, A., and Imbert, D., Chem.Commun., 741, (1986) and Ireland, R.E. and Brown, G., Org.Synthesis, Coll.Vol.V, 428-431).In addition, the reaction that DDQ causes moves (CT) complex compound and can monitor the entire reaction method owing to forming green lotus, when reaction becomes pink gradually, or when brown (because 2,3-two chloro-5,6-dicyano-1, the crystallization of 4-hydrogenation benzoquinones is separated out), illustrate to form target compound.When reaction finishes, sedimentary hydrogenation benzoquinones (DDQH ₂) filter and can easily separate, obtain 2,3-two chloro-5,6-dicyano-1,4-hydrogenation benzoquinones, yield are 90-94%.Can be with standard method expediently with sedimentary quinhydrones (DDQH ₂) change into DDQ, and yield very high (Walker, D. and Waugh, T.D., J.Org.Chem.30,3240, (1965)).Because more than, it is a kind of method with prospects for commercial application that the phenylpropyl alcohol alkane that is caused by DDQ changes into phenylacrolein.In addition, thick oil of Rhizoma Acori Graminei behind the hydrogenation (propenyl-2,4,5-trimethoxy beozene that contains 70-96%) can be directly used in the oxidizing reaction of DDQ and Synthetic 2,4,5-trimethoxy phenylacrolein, can improve income like this, because all the other components in the reductive oil of Rhizoma Acori Graminei can not produce interference in oxidation, and the yield 5-15% that only descends, this depends primarily on the propenyl-2,4,5-trimethoxy beozene content in the oil of Rhizoma Acori Graminei.Therefore, the present invention makes the cost of aforesaid method more cheap.

Therefore, the method for the synthetic phenylacrolein that replaces of the present invention is not only simple, cheapness and yield height, can also transform the multiple substituted benzene propane that is easy to form acid or alkali.

Fig. 1 is the reaction product that contains structure compound as shown in Figure 4 in the example I, 2,4, and 5-trimethoxy phenylacrolein is (at CDCl ₃In) ¹H NMR (300MHz) spectrogram.

Fig. 2 is the reaction product that contains structure compound as shown in Figure 4 in the example I, 2,4, and 5-trimethoxy phenylacrolein is (at CDCl ₃In) ¹³C NMR (75.4MHz) spectrogram.

Fig. 3 is the reaction product that contains structure compound as shown in Figure 4 in the example I, 2,4, and EFI (ES) mass spectrum of 5-trimethoxy phenylacrolein (MW 222).

Fig. 4 is the structure of anti--phenylacrolein of replacement.

Embodiment

The following example is used to confirm the present invention, but the scope that is not intended to limit the present invention.

Initial substance, as p-Propylguaiacol (n-propyl methyl catechol), 3,4-methylenedioxybenzenes propane (dihydro safrol), 4-anisole propane phenylpropyl alkyl derivatives such as (dihydroanetholes), can obtain from commercial source, perhaps from corresponding oxymethoxyallylbenzene, safrol, the shortening respectively of methyl allylphenol derivative obtains (Steffen, A.: perfume and seasonings chemical, Allured Publishing Corporation, 362 South Schmale Road, Carol Steam, IL, USA, (1994)).In addition, 2,4,5-trimethoxy-benzene propane also can or contain the thick oil of Rhizoma Acori Graminei of β-propenyl-2,4,5-trimethoxy beozene by the poisonous β-propenyl-2,4,5-trimethoxy beozene in the Rhizome of Grass leaf Sweelflag and obtain (Sinha, A.K., USP No.09/652, application in 376 2000 on August 31) after the reduction under ammonium formiate is assisted.

Example I

From 2,4,5-trimethoxy-benzene propane Synthetic 2,4,5-trimethoxy phenylacrolein (heating method)

Contain 2,4,70 milliliters of no Shui dioxane solutions of 5-trimethoxy-benzene propane (5 gram) are put into 100 milliliters of round-bottomed flasks.The acetate (2-4 drips) and the 16 gram DDQ that add catalytic amount then, mixture backflow 5-9 hour in 50-140 ℃ of scope at last.Solution begins to be deep green, along with quinhydrones (DDQH ₂) generation become faint yellow.After the mixture cooling, filter and obtain solid DDQH ₂, and wash with chloroform.Merging filtrate and washings, underpressure distillation.Product is used aqueous sodium hydroxide solution (15%, 2 * 15 milliliters) washing mutually with ether (80 milliliters) dissolving, ether.Merge water and use ether (3 * 15 milliliters) extraction again.Merge the ether phase and use saturated sodium-chloride (3 * 15 milliliters) washing, with anhydrous sodium sulfate drying and filtration.Remove the thick product that obtains yellow liquid state after desolvating, on silicagel column,, use more hexane/ethyl acetate (9: 1 to 1: 9) elution again with hexane (70-80 milliliter) elution.With thin-layer chromatography board monitoring separation method, after needed component merged, removal of solvent under reduced pressure obtained 2,4, and the yellow solid of 5-trimethoxy phenylacrolein, yield are 82%; 140 ℃ of fusing points, UV (methyl alcohol) λ maximum 244,298,366nm; Infrared IR (film) ν maximum 1648 (conjugation carbonyls), 1602,1504,1466,1448,1350,1254,1120,1024,856cm ^{-1 1}H NMR δ 9.65 (1H, d, J=7.8Hz, H-3 '), 7.81 (1H, d, J=15.8Hz, H-1 '), 7.03 (1H, s, H-6), 6.64 (1H, dd, J=15.8Hz, J=7.8Hz, H-2 '), 6.51 (1H, s, H-3), 3.95 (s, 3H, 2-OCH ₃), 3.91 (s, 3H, 4-OCH ₃), 3.87 (s, 3H, 5-OCH ₃); ¹³C NMR δ 194.1 (C-3 '), 154.1 (C-1 '), 153.2 (C-2), 147.6 (C-4), 143.3 (C-5), 126.4 (C-2 '), 114.5 (C-1), 110.5 (C-6), 96.5 (C-3), 56.4 (5-OCH ₃), 56.2 (2-OCH ₃), 56.0 (4-OCH ₃); EIMS m/z 222[M] ⁺(44), 207 (18), 191 (100), 179 (14), 171 (27), 151 (14), 147 (7), 69 (58), 58 (80).

Example II

2,4, the permanganate oxidation of 5-trimethoxy phenylacrolein generates asarylaldehyde

Contain 2,4, anhydrous propanone (20 milliliters) solution of 5-trimethoxy phenylacrolein (0.5 gram) is handled with potassium permanganate (0.5 gram).Reaction mixture kept 24 hours in room temperature, removed by filter Manganse Dioxide also except that desolvating.Residue is dissolved in ethyl acetate, and carefully washs with 10% sodium bicarbonate and salt solution, uses anhydrous sodium sulfate drying then.Boil off solvent and obtain solid crude product, the water recrystallization obtains 0.2 gram colorless solid 2,4 again, the 5-TMB, 114 ℃ of fusing points (114 ℃ in document), infrared IR (film) ν maximum 1662 (conjugation carbonyls), 1620,1518,1481,1419,1361,1300,1278,1222,1199,1138,1025,865cm ^{-1 1}H NMR δ 10.32 (1H, s, CHO), 7.33 (1H, s, 6H), 6.50 (1H, s, 3H), 3.98 (3H, s, 2-OCH ₃), 3.93 (3H, s, 4-OCH ₃), 3.88 (3H, s, 5-OCH ₃); ¹³C NMR δ 187.96 (CHO), 158.60 (C-2), 155.76 (C-4), 143.56 (C-5), 117.35 (C-1), 109.03 (C-6), 56.19 (2-OCH ₃, 4-OCH ₃And 5-OCH ₃); EIMS m/z 196[M] ⁺(100), 181 (49), 150 (32), 125 (33), 110 (23), 69 (37).

EXAMPLE III

From β-propenyl-2,4,5-trimethoxy beozene Synthetic 2,4,5-trimethoxy phenylacrolein (heating method)

β-propenyl-2,4,5-trimethoxy beozene (1.87 gram), (0.9 restrains) with contain 0.3 milliliter water in the mixture of diox (30 milliliters) to tin anhydride, refluxes 6 hours.And then adding other a tin anhydride (0.21 gram), mixture continues to reflux 12 hours.After the mixture cooling, remove by filter sedimentary black selenium.The filtrate vapourisation under reduced pressure, residue dissolves with methylene dichloride, uses the salt water washing, uses anhydrous sodium sulfate drying.Boil off solvent and obtain 2; 4; the mixture of 5-trimethoxy phenylacrolein and correspondent alcohol is (when the analogue of some β-propenyl-2,4,5-trimethoxy beozenes carries out allyl oxidation with tin anhydride; usually can form by-product alcohol when generating aldehyde), mixture is directly handled with the excessive pyridinium chloro-chromate that is dissolved in anhydrous methylene chloride (50 milliliters) (1 gram).Stir under the room temperature and spend the night, reaction mixture filters by thin diatomite layer.Filtrate decompression concentrates, and residue column chromatography for separation (petrol ether/ethyl acetate 9: 1 to 1: 9) on silicagel column obtains 52% yellow solid 2,4,5-trimethoxy phenylacrolein; 140 ℃ of fusing points.TLC, CoTLC, physics and spectroscopic data and above trimethoxy phenylacrolein (example I) identical.

EXAMPLE IV

Oxidation 4-anisole propane generates 4-methoxycinnamic aldehyde (microwave irradiation)

Contain 4-anisole propane (2 gram), silica gel (0.5-0.8 gram), (7.5 gram) are with the mixture of diox (5-8 milliliter) adds 100 milliliters of Erlenmeyer flasks to DDQ, and loosening funnel is equipped with on top.Erlenmeyer flask is put into microwave oven, operates 2-8 minute down in mid power (600 watts).Reaction finishes back (monitoring with TLC), in the material impouring chloroform in the Erlenmeyer flask, by diatomite layer, washs with chloroform again.After filtrate and washings merged, chloroform was used aqueous sodium hydroxide solution (15%, 3 * 15 milliliters) washing mutually.Merge water, use chloroform (3 * 15 milliliters) extraction again.Chloroform merges the back mutually with saturated sodium-chloride (3 * 15 milliliters) washing, with anhydrous sodium sulfate drying and filtration.Obtain thick product except that after desolvating, on silicagel column,, use more hexane/ethyl acetate (9: 1 to 1: 9) elution again with hexane (70-80 milliliter) elution.With thin-layer chromatography board monitoring separation method, after needed component merged, removal of solvent under reduced pressure obtained solid 4-methoxycinnamic aldehyde, and yield is 68%; Fusing point 57-58 ℃ (58 ℃ in document).Physics and spectroscopic data are similar to report.

EXAMPLE V

From 3,4-dimethoxy benzene propane synthesizes 3,4-dimethoxy phenylacrolein (heating method)

Contain 3,40 milliliters of no Shui dioxane solutions of 4-dimethoxy benzene propane (1 gram) are put into 100 milliliters of round-bottomed flasks.Add the tosic acid (0.04-0.1 gram) and the 4.5 gram DDQ of catalytic amount then, in 50-140 ℃ of scope, mixture was refluxed 7-16 hour at last.After the mixture cooling, filter and obtain DDQH ₂, and wash with chloroform.After filtrate and washings merge, underpressure distillation.Product is used aqueous sodium hydroxide solution (15%, 2 * 10 milliliters) washing mutually with ether (50 milliliters) dissolving, ether.Merge water and use ether (3 * 10 milliliters) extraction again.Merge the ether phase and use saturated sodium-chloride (3 * 10 milliliters) washing, with anhydrous sodium sulfate drying and filtration.Remove the thick product that obtains yellow liquid state after desolvating, on silicagel column,, use more hexane/ethyl acetate (9: 1 to 1: 9) elution again with hexane (40-50 milliliter) elution.With thin-layer chromatography board monitoring separation method, after needed component merged, removal of solvent under reduced pressure obtained 3, and the yellow solid of 4-dimethoxy phenylacrolein, yield are 79%; Fusing point 74-77 ℃; ¹H NMR δ 9.67 (1H, d, H-3 '), 7.43 (1H, d, H-1 '), 7.15 (1H, d, H-5), 7.08 (1H, s, H-3), 6.91 (1H, d, H-3), 6.61 (1H, dd, H-2 '), 3.94 (s, 3H, 3-OCH ₃), 3.93 (s, 3H, 4-OCH ₃).All the other physics are similar to report with spectroscopic data.

Major advantage of the present invention is:

1) simple and economic commercial run.

2) phenylpropyl alkyl derivatives is changed into the straightforward procedure of corresponding cinnamic acid, and yield High.

3) phenylpropyl alkyl derivatives is changed into the accordingly straightforward procedure of anti--cinnamic acid, because anti-Formula is preferred isomers, often can find in plant.

Toxic compounds β-the asarone that 4) will be meant to forbid or calmus oil or sassafras oil essential oil Deng the method that changes into useful product.

5) introduced serial weld, some of them can't be produced in a large number.

6) synthesis of natural dyestuff is such as 2,4,5-trimethoxy cinnamic acid, as synthetic corresponding The starting material of the simple and inexpensive of acid, ester, pure and mild dihydro alcohol, acid, ester, aldehyde and alkaloid etc. Matter.

7) this chemical method can improve the value of calmus oil, because at present new natural dye The demand straight line rises, and the calmus oil of tetraploid and hexaploid kind (being distributed widely in the Asia) Value with respect to the calamus of dliploid and triploid kind (being distributed widely in America and Europe) The value of oil is low.

8) a kind of method that transforms phenylpropyl alcohol alkane, and phenylpropyl alcohol alkane origin source cheap phenyl widely Propylene bearing essential oil obtains.

9) a kind of can the conversion any aromatic compound that contains the propane side chain or analog Become the straightforward procedure of cinnamic acid.

10) a kind of straightforward procedure of synthetic cinnamic acid, it need not working pressure or explosive reagent.

11) a kind of straightforward procedure of synthetic cinnamic acid, it needs several seconds to number lower of microwave Minute can finish.

12) a kind of straightforward procedure of synthetic cinnamic acid, the purity of its cinnamic acid can further improve by using catalyst, and catalyst is acetic acid, p-methyl benzenesulfonic acid or silica gel etc.,

Claims (23)

1. A substituted trans-cinnamaldehyde with the structure ##STR## shown in Figure 4 synthesized from the corresponding (R ₂ -R ₃ -R ₄ -R ₅ -R ₆ ) phenylpropane derivatives—a natural The method of yellow dye, wherein R ₁ is fixed as -CH=CH-CHO, R ₂ , R ₃ , R ₄ , R ₅ , R ₆ are independently selected from i) a hydrogen atom; ii) an alkoxy group but R ₂ , at least two of R ₃ , R ₄ , R ₅ , and R ₆ are hydrogen atoms or an alkoxy group, but a methylenedioxy group is associated with a hydroxyl group, an alkoxy group, an alkyl group with 1-12 carbon atoms, Arbitrary groups or hydrogen atoms in any combination, or an alkoxy group but a hydroxyl group in any combination with methylenedioxy, hydroxyl, alkoxy, alkyl groups with 1-12 carbon atoms, aryl groups or hydrogen atoms; iii) A methylenedioxy group and at least three of R ₂ , R ₃ , R ₄ , R ₅ , and R ₆ are any of alkoxy, hydroxyl, alkyl with 1-12 carbon atoms, aryl or hydrogen atom Combination; vi) a hydroxyl group but at least one of R ₂ , R ₃ , R ₄ , R ₅ , R ₆ is a hydrogen atom and an alkoxy group, a hydroxyl group, a methylenedioxy group, an alkyl group with 1-12 carbon atoms , aryl or any combination of hydrogen atoms; vii) a protected hydroxyl group such as acetyl, benzyl, but at least one of R ₂ , R ₃ , R ₄ , R ₅ , R ₆ is a hydrogen atom and alkoxy, hydroxyl , methylenedioxy, an alkyl group having 1-12 carbon atoms, an aryl group or any combination of hydrogen atoms; the above-mentioned method comprises using an oxidizing agent to oxidize a substituted phenylpropane derivative in the presence of a solvent and a catalyst, wherein the oxidizing agent is relatively When the molar ratio of the phenylpropane derivative is between 1:1 and 1:8, the reaction is carried out between -15°C and +210°C for 30 minutes to 48 hours, the solvent is removed under reduced pressure, and the product is isolated in a conventional manner to obtain the structural formula The trans-cinnamaldehyde of I, yield is 68-82%. 2. The method according to claim 1, wherein the solvent used is selected from diethyl ether, tetrahydrofuran, dimethoxyethane, dioxane, diphenyl ether, chlorinated solvents such as dichloromethane, chloroform and o-dichlorobenzene, aromatic hydrocarbons Such as benzene, toluene, xylene, and organic acids such as formic acid and acetic acid. 3. The method according to claim 1, wherein the oxidizing agent used is selected from 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), p-chloranil, pyridinium chlorochromate ( PPC), tert-butyl peroxide, chromium trioxide or mixtures thereof. 4. The method according to claim 1, wherein the ratio of oxidant to reactant is between 1:1.5 and 1:5. 5. The method according to claim 1, wherein the reaction temperature is between 30°C and 140°C. 6. The method according to claim 1, wherein the reaction time is between 4-16 hours. 7. The method according to claim 1, wherein the catalyst used is selected from hydrochloric acid, sulfuric acid, Cu(I) or Fe(III) salt, periodic acid, an organic acid selected from acetic acid, propionic acid, butyric acid, selected from IR-120H and sulfonated polystyrene resins are in the group of ion exchange resins, p-toluenesulfonic acid (PTSA) and macroporous resins such as macroporous resin 15. 8. The method according to claim 1, wherein the starting material phenylpropane used is reduced by allylbenzene or phenylpropene derivatives or a wide range of natural allyl/phenylpropene derivatives having three isomers get. 9. The method according to claim 1, wherein trans-cinnamaldehyde is obtained after oxidation of phenylpropane, which is similar to the isomer obtained from plants. 10. The method according to claim 1, wherein toxic β-(cis) or γ-isomers can be converted into high value-added natural dyes. 11. The method according to claim 1, wherein the intentionally prohibited beta-asarone from calamus oil is converted into a useful natural yellow dye. 12. The method according to claim 1, which can produce cinnamaldehyde derivatives on a large scale. 13. The method according to claim 1, wherein the method provides novel cinnamaldehyde derivatives useful as natural colorants, antioxidants and antibacterial agents. 14. The method according to claim 1, wherein the method can provide _DDQH2 (by-product) with a yield of 91-94%, and it can be regenerated into DDQ, saving the cost of producing cinnamaldehyde derivatives. 15. The method according to claim 1, wherein the method can oxidize phenyl alkanes containing 2n-1 carbon atoms to form the corresponding unsaturated aldehydes, wherein n varies between 2-6 or more. 16. The method according to claim 1, wherein said phenylpropane derivatives can be subjected to various reactions such as halogenation, dehydrogenation, allylhalogenation, formylation, mono- and/or dicarbonylation, condensation reactions. 17. The method according to claim 1, wherein the method provides cinnamaldehyde derivatives which are not contaminated with corresponding acids and alcohols. 18. according to the method for claim 1, wherein obtain some cinnamaldehyde with higher yield in this method, as 2,4,5-trimethoxycinnamaldehyde, can be used as synthetic corresponding multiple new unsaturated acid , simple starting material for ester, amide and alcohol derivatives. 19. according to the method for claim 1, obtain some cinnamic aldehydes with the yield that increases in wherein in this method, as 2,4,5-trimethoxy cinnamaldehydes, can be used as synthetic corresponding multiple new dihydro( Saturated) acid, ester, amide and alcohol derivatives are simple starting materials. 20. The method according to claim 1, wherein the product obtained may be (i) 2,4,5-trimethoxycinnamaldehyde, wherein R ₁ is -CH=CH-CHO, R ₂ =R ₄ =R ₅ is -OMe, and R ₃ =R ₆ is H; (ii) p-methoxycinnamaldehyde, wherein R ₁ is -CH=CH-CHO, R ₂ =R ₃ =R ₅ =R ₆ is H and R ₄ is -OMe; and (iii) 3,4-dimethoxycinnamaldehyde, wherein _R1 is -CH=CH-CHO, _R2 = _R5 = _R6 is H and _R3 = _R4 is -OMe. 21. A method for synthesizing substituted trans-cinnamaldehyde with structural formula I, a natural dye, said method comprising using an oxidizing agent and a solid carrier in the presence of a solvent and a catalyst, the molar ratio of the oxidizing agent being between 1-20 During this period, the substituted phenylpropane derivative is oxidized using microwave radiation at a moderate power of 600 watts over a period of 20 seconds to 12 minutes, the solvent is removed under reduced pressure, and the product is isolated in a conventional manner to give trans-cinnamaldehyde of formula I. 22. The method according to claim 21, wherein the solid support is selected from diatomaceous earth, silica gel, molecular sieves and alumina. 23. The method according to claim 21, wherein the product obtained may be (i) 2,4,5-trimethoxycinnamaldehyde, wherein R ₁ is -CH=CH-CHO, R ₂ =R ₄ =R ₅ is -OMe, and R ₃ =R ₆ is H; (ii) p-methoxycinnamaldehyde, wherein R ₁ is -CH=CH-CHO, R ₂ =R ₃ =R ₅ =R ₆ is H and R ₄ is -OMe; and (iii) 3,4-dimethoxycinnamaldehyde, wherein _R1 is -CH=CH-CHO, _R2 = _R5 = _R6 is H and _R3 = _R4 is -OMe.

Images