Preparation coumarin

The bait concentration of warfarin is 0.005% for Norway rats and 0.025-0.05% for black rats or mice. Coumarin preparations are often combined with sulfaquinoxaline (28). This bactericidal substance reduces the bacterial flora producing vitamin K in the intestine. The addition of oil to the bait serves a similar purpose. In this case vitamin K is extracted from the intestine. 

C. Guti rez-Sanchez, V. Calvino-Casilda, E. P ez-Mayoral, R.M. Martin- Aranda, A.J. Lopez-Peinado, M. Bejblova, J. Cejka, Coumarins preparation by Pechmann reaction rmder ultrasormd irradiation. Synthesis of hymecromone as insecticide intermediate, Catal. Lett. 128 (2009) 318 22. 

Coumarin is usually prepared by heating salicylaldehyde with acetic anhydride and sodium acetate (i.e., the Perkin cinnamic acid synthesis, p. 23 6), whereby the 0" hydroxy-cinnamic acid (I) undergoes cyclisation to coumarin. Coumarins having substituents in the benzene ring can often be similarly prepared. 

For the preparation of 4-substituted coumarins, a phenol may be condensed with ethyl acetoacetate under the influence of sulphuric acid. Thus resorcinol (II) readily undergoes this condensation (which is represented diagrammatically above) to give 7-hydroxy-4-methyl-coumarin (III). Note that the coumarins, like all 2 pyrones, are systematically lactones. 

Until the late 1890s, coumarin was obtained commercially from only natural sources by extraction from tonka beans and deer tongue. Then synthetic methods of preparation and industrial manufacturing processes were discovered and developed starting principally from o-cresol, phenol, and sahcylaldehyde. Various methods can be used to obtain coumarin from each of these starting materials. 

The literature had reported the preparation of a coumarin hydroxylamine by the reaction of 4-hydroxycoumarin with hydroxylamine. A reinvestigation of the reaction showed the product to be l,2-benzisoxazole-3-acetic acid (Scheme 172) (69JHC279). 

Al Preparation of 7-Hydroxy-4,8-Dimethy/coumarin Chilled ethyl acetoacetate (157 ml, 1.20 mols) followed by 2-methyl-resorcinol (130 g, 1.04 mols) was dissolved in well-stirred concentrated sulfuric acid (600 ml) at such a rate as to keep the temperature below 10°C (ice bath). The stirred solution was allowed to warm gradually and after 3 hours was added to water (ca 8 liters) with mechanical stirring. The product was collected, washed twice with water, and dried at 70° to 80°C until the first sign of darkening. Yield 191.3 g (95.4%). Recrystallization from aqueous ethanol gave 7-hydroxy-4,8-dimethylcoumarin as colorless needles, MP 260.5° to 261°C. In dilute sodium hydroxide, the compound gives a yellow solution which exhibits blue fluorescence. 

C) Preparation of 6-Allyl-7-Hydroxy-4,8-Dimethylcoumarin 7-Allyloxy-4,8-dimethyl-coumarin (195.0 g, 0.84 mol) was heated (oil bath) to 215 4°C (reaction mixture temperature) for 3 hours and was then poured into absolute alcohol (ca 1.5 liters). Activated carbon (Norite) (19.5 g) was added, and the solution was heated to boiling, filtered, and diluted with excess water (ca 12 liters). The product was collected by filtration and partially dried at 70°C for 6 hours. 6-Allyl-7-hydroxy-4,8-dimethylcoumarin was obtained as pale yellow microcrystalline prisms, MP 166° to 168°C, by two recrystallizations from aqueous ethanol of a portion of the partially dried solid. The remaining partially dried solid was used in the next step. 

Thiourea and allylthiourea (20), D-xylulose (22), sodium diethyldithiocarbamate, L-methionine, and -propyl-di- -propylthiol-carbamate (163), 12 6-(substituted) purines (166), and two coumarin derivatives (164) have been found to promote Striga seed germination. None of these materials, however, appear to be constituents of the natural stimulant preparations. 

AT-Arylquinolin-2(lff)-ones have been prepared in a four step process from commercially available coumarins, utilizing a Buchwald-Hartwig ami-... 

Several coumarin derivatives have revealed pronounced medicinal value as antibacterial and antifungal agents [57,58]. Others have displayed antituber-cular activity [59] and some have insecticidal properties [60]. This prompted us to investigate the preparation of a new series of compounds containing coumarin moieties with different side chains or fused rings. 

Wakselman, M. Hamon, J.-F. Vilkas, M. Lactones phenoliques halomethylees, inhibi-teurs bifonctionnels de proteases II. Preparation de derives halomethyles de la dihydro-3,4-coumarine et de la benzofuranone-2. Tetrahedron 1974, 30, 4069-4078. 

Method B involves the preparation of precursor of 2-alkyl-l-benzo-pyrylium salts, as shown in Scheme ll.50 2-Alkylbenzopyrylium salts have been prepared by condensation of salicylaldehyde with appropriate ketone in acetic acid or by alkylation or reduction of coumarin or chromone derivatives. Reaction of 2-alkylbenzopyrylium salts with salicylaldehyde gives directly a spirodibenzopyran or 2-vinynologue benzopyrylium salt 17 which then can be converted into the spirodibenzopyran by piperidine or pyridine. 

The 2,2-dialkylchromenes can easily be obtained from the reaction of coumarin 27 with a Grignard reagent.48 This method has been known for a long time and has not been modified much. The parent chromene 28 has been prepared by reduction and dehydration of 4-chromanone.63 Elimin-... 

Metljylcoumarone has been prepared by the cyclization of ethyl a-phenoxyacetoacetate followed by hydrolysis and decarboxylation of the resulting ethyl 3-methylcoumarilate,3 4 by debromination and rearrangement of 3,4-dibromo-4-methyl-coumarin to 3-methylcoumarilic acid followed by decarboxylation,4-6 by cyclization of phenoxyacetone with concentrated sulfuric acid,6 and by treatment of 3-coumaranone with methyl-magnesium iodide followed by dehydration of the resulting car-binol.7... 

Most of the important class of coumarins used as polyester FBAs are made via 7-amino-3-phenylcoumarin (11.46), which can be prepared by the Pechmann procedure from m-aminophenol. Conversion of intermediate 11.46 to FBAs may be achieved in various ways, two of which are shown in Scheme 11.13. 

Synthesis of the coumarin derivative 11.58 containing two isomeric triazolyl rings is indicated in Scheme 11.24- The substituted pyrazolyl derivative of naphthalimide 11.59 is prepared by a reaction sequence somewhat similar in principle to that already shown in Scheme 11.14, using 4-amino-1,3,5-trimethylpyrazole in the penultimate step followed by quaternisation. 

Hydroxycoumarins and 4-hydroxyquinolinones have also been applied as 1,3-dicarbonyl compounds. Using these compounds, Raghunathan and coworkers prepared pyrano[3,2-c]coumarins [387] and pyranoquinolinones [388] under traditional conditions, while the group of Yadav synthesized similar pyrano[3,2-c]coumarins employing ionic liquids as solvents [389]. 

Recently, chloromethylated benzocoumarin 11c, hydroxylmethylated benzocou-marin 12, and chloromethylated coumarin 13 were used in the efficient preparation of several fluorescent ester conjugates of /V-benzyloxycarbonyl-neurotransmitter amino acids, such as p-alanine, tyrosine, 3,4-dihydroxyphenylalanine (DOPA), glutamic acid, and y-aminobutyric acid (GABA) [39, 40],... 

Brufola G, Fringuelli F, Piermatti O, Pizzo F (1996) Simple and efficient one-pot preparation of 3-substituted coumarins in water. Heterocycles 43 1257-1266... 

Coumarilic add has also been prepared by Perkin from 3-chloro-coumarin and from 3-bromocoumarin by the action of alcoholic potassium hydroxide.2... 

Coumarin dibromide has been prepared by the addition of bromine to coumarin in chloroform solution. 1-2... 

Methylcoumarin is prepared by the condensation of phenol and acetoacetic ester. Concentrated sulfuric acid1,2 and 73% sulfuric acid have been used.3 4 The method given here was mentioned by Sethna, Shah, and Shah,6 and the procedure is adapted from that of the same authors 6 for another coumarin derivative. 

Coumarilic acid has been prepared by treating coumarin dibromide with alcoholic potassium hydroxide and acidifying with hydrochloric acid, a method due essentially to Perkin.1... 

Triazinothiadiazines 24 and 25 <2002IJH287> containing sydnone and coumarin systems have also been prepared from 4-amino-3-mercapto-6-substituted-l,2,4-triazin-5-ones 38 as shown in Scheme 5. 

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