The alkali can also be applied as a mixture of two or more. The HPLC method used for determination of cinnamic acid in human plasma used C18 column and the mobile phase was acetonitrile- 0.1 mol/L KH 2PO 4 solution (30:70) at flow rate 1.2 ml/min the UV detection wavelength was 272 nm were used [15-17]. 0 Therefore, procedures such as extraction and concentration are required for the isolation of desired products. Standard Preparation. Hence the cinnamic acid having good quality can be obtained efficiently and in good yield. 0000001824 00000 n In the process of this invention, the cinnamic acids can be precipitated by acidifying the resultant aqueous alkaline solution with mineral acid so that the reaction mixture forms a slurry or suspension. R4 represents unsubstituted or substituted alkyl group.). On the other hand, the alkali hydrolysis is, as described above, commonly carried out in a homogeneous system employing the aqueous mixture of organic solvents. As a result, the separated cinnamic acid was 85.5 grams and the yield was reduced to 93.5%. It is a member of styrenes and a member of cinnamic acids. In order to afford high yield of the cinnamic acid in the method of this invention, the alkali cinnamate and the mineral acid are required to react so as to keep the pH value at not more than 4 and preferably at not more than 3 in the solution after ending the acidification reaction. 33 0 obj<>stream is acid possessesantibacterial,elevatedwhitebloodcell,cholagogue, and anticancer e ects [] . In the category of phytochemicals that can be found in food, there are : . Therefore it becomes difficult to conduct the acidification of aqueous solution of the alkali cinnamate with the mineral acid in a high concentration and the amount of products produced per unit volume of the reaction vessel is reduced. 0000001218 00000 n The cell pellet was washed twice with 25 mM potassium phosphate buffer of pH 7.0 and resuspended in the same buffer. This UPLC-DAD method was developed and validated for simultaneous quantitation of coumarin, trans-cinnamic acid, trans-cinnamaldehyde, and eugenol. 0000001089 00000 n J Chromatogr Sci. In this study, trans-cinnamic acid (CA) was used as a representative substance of goreisan constituents, and assayed by HPLC-UV. Almost all of the compounds showed some inhibition activity on each of the fungi at 0.5 mM. In all cases, small amounts (<10% yield) of meso hydrodimers were also formed. A 1 &litre round bottomed flask equipped with a stirrer was charged with 100.0 grams (0.617 mol) of methyl cinnamate and 700 grams of aqueous solution containing 25.9 grams (0.647 mol) of sodium hydroxide and vigorously stirred for 15 minutes at 80°C. This novel approach allows the preparation of various cinnamic acids in good to high yields (up to 81%). 1a) and its simple derivatives are widely represented in plants. I have already done a Doebner reaction using using benzaldehyde and malonic acid. In the acidification of this invention, the batchwise or semi-batchwise operation wherein the aqueous solution of alkali cinnamate is added into the mineral acid, or the continuous operation wherein the reaction is conducted by maintaining the pH value of the system at not more than 4, has the advantage of performing the acidification in the higher concentration of the produced cinnamic acid in the suspension. This novel approach allows the preparation of various cinnamic acids in good to high yields (up to 81%). Otherwise the system becomes a slurry having a high viscosity during acidification and in extreme cases stirring is inhibited by solidification of the total system. The same reaction procedure as in Example l was carried out except 230 grams of water was used in hydrolysis. The same reaction procedure as in Example l was carried out except 17.6 grams (0.1 mol) of ethyl cinnamate was used in place of methyl cinnamate. The electrolysis was performed conveniently using an undivided cell at a constant current. It was validated to be specific, precise, and accurate for the detection and quantitative assessment of these four constituents in encapsulated cinnamon flavoring powder. Cinnamic acid is a monocarboxylic acid that consists of acrylic acid bearing a phenyl substituent at the 3-position. Method: It is well-known that Verley-Doebner modification is a high efficient method for the preparation of cinnamic acid derivaties, especially with the compounds containing electron-donating subtituents at para position in aromatic ring. The concentration of cinnamic acid in the reaction vessel was about l0 wt.%. It is found in Cinnamomum cassia. Experiment 5: Preparation of Trans-cinnamic Acid from Malonic acid and Benzaldehyde with the Knoevenagel reaction. Triethylamine and phos-phoric acid were analytical grade, and methanol and acetonitrile were chromatographic grade. Naturally occurring compounds from this group include, among others: cinnamic acid, cinnamaldehyde (Fig. The aim of this study to purified the cinnamic acid from the cinnamon bark. Cinnamic acid was prepared by oxidation of benzalacetone which was synthesized by condensing benzaldehyde and acetone. In contrast to classic methods (cf. When the acidification of aforementioned aqeuous alkaline solution is conducted either by adding the aqueous alkaline solution into mineral acid or by continuously charging the aqueous alkaline solution and said mineral acid into the reaction vessel so as to keep the pH value at not more than the specific value in the mixture obtained by acidifying and continuously discharging the product, this method can decrease the quantity of water in use, and thus the amount of product produced per unit volume of the reaction vessel can be increased, the environmental problems on drainage is mitigated, the loss of the product by dissolving in the drainage is reduced and the cinnamic acids having an excellent qualify can be obtained in good efficiency. For the determination of Phenylalanine Ammonia-lyase (PAL) Activity, I have to prepare standard curve of cinnamic acid, but I am not finding the right protocol for the preparation of standard curve. Preferably the whole binary-phase system is substantially free of organic solvents. 3 The resulting solution is chilled, cinnamic acid gets separated as colourless crystals, filtered in the Buchner funnel, washed with a little cold water, drained well and dried at 100 °C. The samples were separated by a LiChrospher RP-18 column with water-acetonitrile-methanolacetic acid (61:34:5:0.1 or 80:15:5:0.1, v/v) as t … The cinnamate esters useful for the practice of the process of this invention comprise those of the following formula: (wherein n is an integer of l to 5, R1 is hydrogen or at least one kind of substituent on the aromatic ring and represents, for example, halogen, hydroxyl, alkyl of l to 4 carbon atoms or alkoxy of l to 4 carbon atoms. The cinnamic acid preparing process includes the following steps: mixing 1, 1, 1, 3-tetrachloro-3-phenyl propane as material and one ionic liquid of imidazole, quaternary amine, pyridine or quaternary phosphine in the molar ratio of 1 to 0.25-10, and heating in oil bath at 80-190 deg.c to form homogeneous or inhomogeneous system adding water in the molar amount of 1.1 times the material for hydrolysis to … Therefore the method of this invention is technically very advantageous for preparing the cinnamic acid. The cinnamic acids can be separated from the mixture by suitable means, for example, filtration, and decantation. The purpose of this study was to develop a sensitive method for quantifying cinnamic acid in human plasma using UPLC–ESI–MS/MS. Besides the acidification reaction of this invention is also preferably conducted by the continuous operation. All the stock solutions were stored in a refrigerator at 4°C. The main advantage of the method we present is the Therefore, recovery of the organic solvents is not required and easy separation of the resultant cinnamic acid can be attained. α-Cyano-4-hydroxycinnamic acid; Caffeic acid – burdock, hawthorn, artichoke, pear, basil, thyme, oregano, apple by the' Stuart-method ' of heating o-chlorobenzaldehyde with malonic acid and glacial acetic acid. Consequently, cinnamic acid obtained was 14.4 grams (97.2% yield) and had purity of above 99.9%. Preparation of cell free extract and enzyme assays. 12736/'85). The yield was low though. The term continuous operation mentioned herein is different from what is called batchwise operation in which raw materials are charged in a lump and discharged after ending the reaction. 0000018061 00000 n After charging about 20 grams of sulfuric acid in the flask in advance, the aqueous alkaline solution of sodium cinnamate was added dropwise with stirring until pH of 2 was indicated. The aqueous alkaline solution of sodium cinnamate thus obtained was added slowly under stirring into 200 ml of aqueous sulfuric acid solution containing 0.056 mol of sulfuric acid. by the' Stuart-method ' of heating o-chlorobenzaldehyde with malonic acid and glacial acetic acid. 0000000016 00000 n Privacy Policy The electroreduction of Ar-substituted methyl cinnamates in acetonitrile gave all-trans cyclized hydrodimers stereoselectively (58∼90% de). For producing benzalacetone, benzaldehyde was reacted with acetone in 1% NaOH solution. 1b), cinnamyl alcohol (Fig. Sodium hydroxide or potassium hydroxide is preferably employed among these compounds. The present inventors have made an intensive effort on the study of alkali hydrolysis of cinnamate esters to render the above objects achievable. The procedure of Example l was repeated except 2000 ml of aqueous sulfuric acid solution containing 0.085 mol of sulfuric acid were used in place of the aqueous acid solution in acidification. 0000002417 00000 n The reaction temperature is preferably in the range of 40 to 120°C and more preferably 60 to 100°C. The procedure of Example l was repeated except 6.9 grams of 85% potassium hydroxide was used in place of sodium hydroxide in hydrolysis. Preparation of cell free extract and enzyme assays. It has a role as a plant metabolite. The suspension of the cinnamic acid formed by the acidification of this invention is continuously discharged, and optionally, it may be discharged intermittently. Experiment 5: Preparation of Trans-cinnamic Acid from Malonic acid and Benzaldehyde with the Knoevenagel reaction. The benzalacetone was further oxidized with sodium hypochlorite to give 88.2% of cinnamic acid, m.p. For example, quantity of the raw materials can be set so as to obtain the pH value of not more than 4 after the reaction. The present invention is further illustrated by the following Examples and Comparative examples. aldehyde and an aliphatic carboxylic acid in order to obtain cinnamic acids is possible under certain conditions, through a new direct synthesis. 6 to < 2 log cfu g −1 for 21 d at 4°C; however, undesirable colour and odour changes were also observed. 8.6 [140]. Consequently cinnamic acid thus obtained was 14.6 grams (98.5% yield) and had purity of above of 99.9%. The precipitates were filtered with suction, washed with 50 ml of water by stirring in a beaker, filtered again and dried under reduced pressure. : 133 oC) was first melted and heated in an oven at 180 oC for 30 minutes. In support of the Krubsack mechanism, when an electron-releasing group, such as methoxy, was present on the benzene ring, … trans -Cinnamic acid (TCD, also known as trans --pheny-lacrylic acid) is one of the main chemical constituents of cinnamon which belongs to plant Lauraceae [, ]. 0000007639 00000 n A process of preparing a cinnamic acid by hydrolyzing a cinnamate ester represented by the following formula: Click for automatic bibliography The resulting cinnamic acid is then precipitated by addition of a mineral acid. The quantity of cinnamic acid produced was 116 g/&litre to one liter of water used, and about 700 g/&litre to the unit volume of reaction vessel. The present invention provides a process of preparing a cinnamic acid by hydrolyzing a cinnamate ester represented by the following formula: (wherein: Ar is an optionally substituted benzene ring; R² and R3 may be the same or different groups and represent respectively hydrogen or alkyl of 1 to 6 carbon atoms; and R4 represents an unsubstituted or substituted alkyl group) with an alkali in a heterogeneous binary-phase liquid system using water as a solvent to obtain an aqueous alkaline solution of an alkali cinnamate, characterised by starting said hydrolysis reaction in a heterogeneous binary-phase liquid system, which consists of a melted cinnamate ester and an aqueous alkali solution, using the water in such quantity that the concentration of the alkali cinnamate is 1 to 20% by weight in the aqueous alkaline solution; and precipitating the cinnamic acid by conducting an acidifying reaction of said aqueous alkaline solution with a mineral acid, under such conditions that the pH value of the resulting liquid after completion of the acidifying reaction is kept at not more than 4 and that the concentration of the produced cinnamic acid when the reaction is completed is 1 to 20% by weight of the resulting suspension; said acidifying reaction being conducted either by adding the aqueous alkaline solution of the alkali cinnamate obtained by the hydrolysis reaction into the mineral acid or by continuously charging the aqueous alkaline solution of the alkali cinnamate obtained by the hydrolysis reaction and the mineral acid into an acidifying reaction vessel, followed by continuously discharging the resulting liquid containing the cinnamic acid precipitated therein from said reaction vessel. The alkali for use in the alkali hydrolysis of this invention includes, for example, sodium hydroxide, potassium hydroxide, calcium hydroxide and barium hydroxide. Access to the cinnamic acids 7a-k and the targeted (E)-styrylthiazoles 4a-g and the (E)-2-[2-(naphthalen-1-yl)viny]thiazoles 4h-l, all of which satisfy the “Lipinski rule of 5”,19 is outlined in Scheme 1. For instance, these processes are methods of preparing cinnamic acid and its derivatives from benzaldehydes as a main raw material by Perkin reaction, Knoevenagel reaction or Claisen condensation (as described in, for example, Organic Reactions, vol. Besides, the following facts have also been found. It can also inhibit melanoma and proliferation and promote di erentiation of cancer cell in Stenotrophomonas sp. hydroxybenzoic acid. Commercially available trans-cinnamic acid (m.p. Cinnamic acid is a monocarboxylic acid that consists of acrylic acid bearing a phenyl substituent at the 3-position. Consequently, cinnamic acid obtained was 14.5 grams (97.9% yield) and had purity of above 99.9%. It means the operation of discharging the reaction product while charging the raw materials. A separable flask equipped with a stirrer was charged with 16.2 grams (0.10 mol) of methyl cinnamate, and a solution of 4.3 grams of 97 wt.% sodium hydroxide in 200 grams of water, and the mixture was reacted at 80°C for 15 minutes with vigorous stirring. CGWW, pp 703 Background: Those reactions that are called aldols derive their name from the early nineteenth-century organic literature. : 133 oC) was first melted and heated in an oven at 180 oC for 30 minutes. The partial purified cinnamic acid is obtained after column chromatography application. Cinnamic acid and its derivatives have a numerous potential applications in many different fields such as pharmacy, organic “building blocks”, and corrosion inhibitors. For producing benzalacetone, benzaldehyde was reacted with acetone in 1% NaOH solution. In the present study, the continuous pH-gradient elution was employed in HSCCC. Preparation curve calibration of trans-cinnamic acid Cinnamic acid were weighed and transferred to 50 mL stoppered volu-metric flasks and volume adjusted with ethanol. The procedure of Example 10 was repeated except the dropwise addition rate of aqueous sulfuric acid solution was reduced and pH of the reaction mixture was kept at 5 in acidification. It is also desirable to provide a method of preparing a cinnamic acid by starting the hydrolysis of the cinnamate ester with the alkali in the heterogeneous binary-phase liquid system, followed by acidifying the resultant alkaline solution with the mineral acid through an improved method. Commercially available trans-cinnamic acid (m.p. That is, the yield of the product reduces at less than 1% by weight, while a highly concentrated slurry is formed at more than 20% by weight and causes insufficient stirring, incomplete reaction and deterioration in the purity of product. METHOD: The ability of catching oxygen of the products and raw material were determined through two methods, Marklund method and trace pyrogallic acid method, with autoxidation reaction of … The procedure of Example l was repeated except 64 grams of water were used in the hydrolysis. Cinnamic acid obtained was 14.7 grams (99.9% yield). Both methods gave products in similar yields. Therefore the acidification reaction of the alkali cinnamate solution is suitably carried out by maintaining the system always in acidic conditions, that is, at the pH value of not more than 4 and preferably not more than 3. Any of these operations can be applied. The solvent system composed of n-propanol and am­ monia (70: 30) was employed to separate cinnamic acid and benzoic acid from p-hydroxybenzoic acid. Cinnamic acid was separated using water containing 0.005% (v/v) formic acid and acetonitrile as a mobile phase by gradient elution at a flow rate 0.2 mL/min, equipped with a HALO-C18 column (2.1 × 100 mm, 2.7 μm). 50611/'72, Japanese Patent Laid-Open No. These materials form much less intense photochemically generated adduct peaks in the protein quasimolecular ion signal and the adduct peaks that are present are easier to resolve. Curve calibration pre-pared from standar solution of trans-cinnamic acid containing 0.5-2.5 µg/mL. The total reaction mixture was discharged and filtered with suction. Consequently cinnamic acid thus obtained was 14.5 grams (97.9%) and had purity of above 99.9%. The solution was added dropwise with stirring to a beaker having 20 ml of aqueous sulfuric acid solution containing 0.053 mol of sulfuric acid. Besides a method has also been proposed recently wherein styrene or its derivatives are reacted with carbon monoxide, alcohol and oxygen in the presence of a catalyst (as described in Japanese Patent Publication Nos. Blacklight irradiation the Furthermore, the solvents used for the extraction should be recovered in the industrial application. Vigorous stirring is more effective for the acidification. As a result the product is deteriorated in quality and the yield tends to decrease. Cinnamic acid thus obtained was 90.0 grams (98.5% yield) and had purity of above 99.9% according to the analysis of liquid chromatography. 31 0 obj<> endobj The yield was 88.8% of the theoretical. Cinnamic acid thus obtained was 14.6 grams (98.5% yield) and had purity of more than 99.9% according to analysis. The concentration outside of this range cannot sufficiently achieve the object of this invention. For example, as aforesaid, these can be prepared by Claisen condensation from benzaldehydes and acetate ester, by the oxidative carbonylation reaction of styrene compounds, by the reaction of benzene or its derivatives with acrylate ester and further by the separation from natural storax. The procedure of Example l was repeated except 0.112 mol of hydrochloric acid was used in place of 0.056 mol of sulfuric acid in acidification. Determination of cinnamaldehyde, cinnamic acid, paeoniflorin, glycyrrhizin and [6]-gingerol in the traditional Chinese medicinal preparation Kuei-chih-tang by cyclodextrin-modified micellar electrokinetic chromatography Hsi-Ya Huang, Kuang-Lung Kuo, You-Zung Hsieh* The procedure of Example 6 was repeated except 6.9 grams of 85 wt.% potassium hydroxide in place of sodium hydroxide. The embodiments of acidification reaction are, for example, the operation of adding said mineral acid into the aqueous alkaline solution of alkali cinnamate, the operation of adding the aqueous alkaline solution of alkali cinnamate into the mineral acid and the operation of continuously charging both components. CGWW, pp 703 Background: Those reactions that are called aldols derive their name from the early nineteenth-century organic literature. The purpose of this study was to develop a sensitive method for quantifying cinnamic acid in human plasma using UPLC–ESI–MS/MS. The procedure of Example 6 was repeated except 17.6 grams (0.1 mol) of ethyl cinnamate was used in place of methyl cinnamate. 0000007341 00000 n tional method; mangiferin, jateorrhizine, palmatine, berberine, cinnamic acid, and cinnamaldehyde were all ordered from the National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China). 0000010308 00000 n Carefully, the filtrate is rendered to acidic pH by adding concentrated HCl gradually in small lots at intervals, and with continuous shaking until the evolution of CO 2 ceases completely. The reaction pressure is normally atmospheric and yet in some cases slightly decreased or increased pressure is effective. OBJECTIVE: To prepare cinnamic acid derivatives-g-CTS and to study its antioxidation activity. Cinnamate esters are always formed as an intermediate in such processes as Claisen condensation which used benzaldehyde and acetate esters, a method of using benzene or its derivatives and acrylate esters as the raw materials, and a method of employing styrene or its derivatives, carbon monoxide, alcohol and oxygen as the raw materials. 133°C. 0000003521 00000 n 2.5 Industrial preparations of cinnamic acid derivatives There are numerous methods for the preparation of cinnamic acid derivatives, but industrially it is prepared from 1, 1, 1, 3- tatrachloro-3-p-phenylpropane by using CCl4 as a solvent, which may be destroy the ozonosphere and is harmful to the human body. Cinnamic acid, benzoic acid and p-hydroxybenzoic acid were determined spectrophoto­ metrically after separation on paper chromatogram. The separation step of the cinnamic acid from the suspension may be carried out batchwise or continuously. An aqueous alkaline solution of sodium cinnamate was obtained by the same method as described above. The developed HPLC methods are summarized in table (1) Cinnamic acid and Cinnamic acid derivatives Background and objective: Periodontitis is the chronic destructive disease of the periodontium, which causes severe inflammation in the tissues. It is found in Cinnamomum cassia. The mineral acid includes, for example, hydrochloric acid, sulfuric acid and phosphoric acid. 2. It is a member of styrenes and a member of cinnamic acids. The yield was 88.8% of the theoretical. conditions, through a new direct synthesis. ), our alternative uses aliphatic carboxylic acids instead of the corresponding anhydrides. The procedure of Example l0 was repeated except 19 wt.% hydrochloric acid was used in place of 25 wt.% sulfuric acid and pH was kept at not more than 3 in the reaction vessel in acidification. One of the simplest and most efficient and environmentally benign methods for cinnamic acid synthesis is based on the Knoevenagel condensation of diethylmalonate with benzaldehyde catalyzed by mixed oxides of Mg/Al, Mg–Al + Ln (Ln = Dy, Gd), or Li/Al as shown in Fig. The purity was above 99.9% according to analysis. In the acidification reaction of aqueous alkaline solution of the alkali cinnamate by the method of this invention, the quantity of water in use is adjusted so that the concentration of the produced cinnamic acid is 1 to 20% by weight and preferably 2 to 15% by weight of the suspension. Some embodiments of the invention will now be described in greater detail. Cinnamic acid as an unsaturated carboxylic acid might prevent inflammation and periodontal destruction. 5570/'84 and 23661/'85). It is well-known that Verley-Doebner modification is a high efficient method for the preparation of cinnamic acid derivaties, especially with the compounds containing electron-donating subtituents at para position in aromatic ring. xref Cinnamic acid is a central intermediate in the biosynthesis of a myriad of natural products including lignols (precursors to lignin and lignocellulose), flavonoids, isoflavonoids, coumarins, aurones, stilbenes, catechin, and phenylpropanoids. 2004 Apr;42(4):207-10. Primaquine-Cinnamic Acid Conjugates of the Amide ... Two methods for the preparation of amides 3a k were applied: acid chlorides 4 (method A) and benzotriazolides 2 (method B) were used as the activated CAD intermediates. Consequently, cinnamic acid obtained was 13.9 grams and the yield was reduced to 93.8%. Then the resultant aqueous alkaline solution of sodium cinnamate having concentration of 13.1% by weight was transferred to a hot dropping funnel kept at 80°C. In the prior arts, mineral acids are added to the aforesaid alkaline solution of alkali cinnamate containing the organic solvents. 133°C. So this is the main drawback of EP-A-165,521 discloses a process in which a mixture in which the principal ingredient is a cinnamate ester is hydrolysed with aqueous base, for example sodium hydroxide or potassium hydroxide. After heating for 15 minutes with stirring, the flask was fitted with a Liebig's condenser and further heated to give 30 grams of distillate. UNIV ZHEJIANG. 102614/'74). 0000003232 00000 n An example of the effective manner for removing alcohol is to distill generated alcohol out of the system together with exhaust gas by feeding inert gas into the reaction solution. Cinnamic acids are technically important as materials for perfumes, photosensitive polymers and various organic or biochemical products. Herein, we report a simple, dependable, and scalable preparation method for CBDA-4 (Scheme 1). The term was first applied to a … A high-performance liquid chromatographic method for the determination of cinnamic acid in Cinnamomi ramulus and paeoniflorin in Paeoniae radix was established. Coumarin and trans-cinnamic acid were purchased from Sigma-Aldrich. When the pH value is more than 4, precipitation of the desired product is incomplete even in acidic conditions and thus the yield is reduced.