Acids from Coumarins

Cinnamic acids can be created from the methylation of coumarins. Methoxy substituted coumarins produce lower yields than do non-substituted and hydroxy substituted coumarins. 

5 Moles of substituted coumarin is mixed with 65 mL of dimethyl sulfate and 70 mL. of 33% potassium hydroxide. The reaction is allowed to complete, cooled and mixed with more dimethyl sulfate and potassium hydroxide. The reaction mixture is refluxed with 150 mL of 33% potassium hydroxide for one hour. The reaction mixture is then methylated further with more dimethyl sulfate. Potassium hydroxide is added again and refluxed to hydrolyze the methyl estev that is formed. The solution is then mixed with 3 liters of water and filtered through charcoal. The mixture is chilled, mixed with hydi i) chloric acid to precipitate the cinnamic acid which is collected by vacuum filtration. 

Starting Molecule 6-Hydroxy 4-methylcoumarin Product 2,5-Dimethoxy-B-methylcinnamic acid Reference Woodruff 1942 

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Mercuric oxide potassium hydroxide Coumarilic acids from coumarins... 

Benzo[b]furan-2-carboxylic acids bromination, 4, 602 chloromethylation, 4, 602 from coumarins, 3, 686 IR spectra, 4, 590 methyl ester... 

Coumarin was first produced synthetically by Perkin. He made it by heating salicylic aldehyde, CgH (OH)i(COH), acetic anhydride, and sodium acetate. The whole solidifies to a crystalline mass, from which, on treatment with water, an oil separates containing coumarin and aceto-coumaric acid. This acid on heating is decomposed into acetic acid and coumarin, so that the product of distillation is principally coumarin. Perkin s synthesis proceeds according to the following equation —... 

The 12-membered macrocyclic triamine bearing a phenol pendent (591) was synthesized by one-pot annealation from coumarin and l,7-diamino-4-azaheptane. Upon coordination to Ni, the pendent phenol readily dissociates its proton at acidic pH and becomes a strong fourth donor.1506... 

Perkin WH (1877) Formation of coumarin and of cinnamic and of other analogous acids from the aromatic aldehydes. J Chem Soc 31 388—427... 

Coumarin (7.88) is a well-known 6-lactone (six-membered ring) of natural origin found in various preparations such as some tobaccos, alcoholic beverages, and cosmetics. Besides reactions of oxidation, reduction, and conjugation, coumarin is also subject to lactone hydration in vivo and in the presence of microsomes [170-174], The resulting metabolites include ortho-coumaric acid (7.89) formed directly from coumarin, 3-(2-hydroxyphenyl)-propionic acid (7.91) formed following reduction of coumarin to dihydrocou-... 

Phenylalanine Ammonia-Lyase. The building units of lignin are formed from carbohydrate via the shikimic acid pathway to give aromatic amino acids. Once the aromatic amino acids are formed, a key enzyme for the control of lignin precursor synthesis is phenylalanine ammonia-lyase (PAL) (1). This enzyme catalyzes the production of cinnamic acid from phenylalanine. It is very active in those tissues of the plant that become lignified and it is also a central enzyme for the production of other phenylpropanoid-derived compounds such as flavonoids and coumarins, which can occur in many parts of the plant and in many different organs (35). Radioactive phenylalanine and cinnamic acid are directly incorporated into lignin in vascular tissue (36). 

An example of anomalous behavior in closely related systems was reported some time ago during an investigation of the cychzation products derived from coumarin semicarbazones (Scheme 6.21). Thus, 78a reacted cleanly with chloro-acetic acid to yield 79a, which cyclized to the expected product 80a upon treatment with sodium acetate. On the other hand, 79b did not cyclize under the same reaction conditions. This was attributed to the absence of the enolizable hydrogen (Ph vs. H). The authors did not comment on the possibility of cyclization of 79b to 80b. The closely related urea analogue 81 did not react with chloroacetic acid thereby... 

R = R = Me) which are obtained by photooxidation of the corresponding olefin.72 The acid-induced cyclization of the same alcohols has been used they are prepared from coumarins 87,88,185,186 or by base-promoted elimination from epoxides (50).150,164 The acid-catalyzed equilibrium between these alcohols and the corresponding... 

A similar pathway is thought to be involved in the synthesis of chromenes from coumarin (see Section 2.23.6.4.1), whilst the spontaneous dehydration of the alcohol (97) to the ketochromene (98), which occurs during acid hydrolysis, also presumably proceeds through the same type of intermediate. This step is an important feature of the synthesis of siccanochromene A, a fungal metabolite, from orcinol and the aldehyde (96) outlined in Scheme 10. Another point of interest in this route is the use of heteroatom-facilitated metallation to achieve the correct orientation (71T6073). 

When heated with polyphosphoric acid, 2-ethoxychromans lose ethanol to give the chrom-2-ene (67CB1296). The method constitutes a synthesis of chrom-2-enes from coumarins, since the chromans are obtained in two steps from the latter. 

The formation of 2-oxopyran-5 -carboxylic acid (coumalic acid) from 2-hydroxybutanedioic acid (malic acid) is described in detail (63OSC(4)20l) and involves the decarbonylation and dehydration of the hydroxy acid. The formylacetic acid so formed then undergoes selfcondensation. This synthesis is an example of the Pechmann reaction usually associated with the synthesis of coumarins (benzopyran-2-ones). It will be observed that this route leads to pyran-2-ones which carry identical substituents at the 4- and 6-positions. 

Tannins and lignins are also derived from these pathways but are not included in Table 1. To make the list as simple as possible, all compounds of aromatic nature, viz., simple phenols, benzoic and cinnamic acid derivates, coumarins, flavonoids and quinones are condensed into one group - aromatic compounds. Thus I will attempt to cover systematically the secondary plant growth substances that fall into 11 major groups as shown in Table 1. 

Coumarins are readily accessed via the Pechmann condensation of phenols and 1,3-dicarbonyl compounds, which proceeds via electrophilic aromatic substitution of the phenol followed by dehydration and lactonization <1984CHEC, 1996CHEC-II>. In this manner, the amino acid bearing coumarins 676 are formed by a Pechmann condensation of phenols and 2-amino-6-ethoxy-4,6-dioxohexanoic acid 677 (Scheme 161) <2004AGE3432>. The popularity of this approach results from the wide range of readily available substrates (phenols and 1,3-dicarbonyl compounds). However, a major drawback is that electron withdrawing groups on the phenolic component dramatically reduces the yield of a Pechmann reaction. 

PROP The constituents include d-a-terpineol, butyl dihydrophthalides, butyl tetrahydrophthalides, coumarin, aldehydes, acetic acid, and isovaleric acid. From steam distillation of fresh root of Ijevisticum officinale L. Koch syn. Angelica levisticum, Baillon (Fam. Vmbelliferae). Yellow to green to brown liquid strong odor and taste. D ... 

Coumarins are known to react with amines to give various products, for example 2,3-dihydrobenzofurans. 3-Bromocoumarin has been shown to give the benzofuran (194) on heating with piperidine but coumarin itself gave 2 -hydroxycinnamic acid amides. The behaviour of coumarin-3-carboxylic acid with amines depends on the ratio of reactants and the temperature. When 8-acetyl-7-hy(iroxy-4-methylcoumarin was subjected to a Mannich reaction, the benzodipyran (195) was formed in 80% yield.Several other tricyclic products have been prepared from coumarins for example, the... 

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