Methyl-7-hydroxycoumarin

A simplified procedure is possible by using polyphosphoric acid as the condensing agent. Add 160 g. of polyphosphoric acid to a solution of 11 g. of resorcinol in 13 g. of ethyl acetoacetate. Stir the mixture and heat at 75-80° for 20 minutes, and then pour into ice-water. Collect the pale yellow solid by suction filtration, wash with a little cold water, and dry at 60°. The yield of crude 4-methyl-7-hydroxycoumarin, m.p. 178-181°, is 17 g. Recrystalbsation from dilute ethanol yields the pure, colourless compound, m.p. 185°. 

Coumarin itself has a poor quantum yield, but appropriate substitution leads to fluorescent compounds emitting in the blue-green region (400-550 nm). Substitution in position 4 by a methyl group leads to umbelliferone. 7-Hydroxycoumarins are very sensitive to pH. For example, 4-methyl-7-hydroxycoumarin (4-methyl-umbelliferone) can be used as a fluorescent pH probe (see Chapter 10). 

A derivative of coumarin that has been extensively used for intracellular pH measurement is 4-methylumbelliferone (4-methyl-7-hydroxycoumarin) because of its pKa value of 7.8, the relatively large variation in its fluorescence intensity versus pH, and its low toxicity. Excitation ratio measurements at 365 and 334 nm with observation at 450 nm permit a six- to ten-fold increase over the pH range from 6 to 8. 

Resorcinol condenses similarly with ethyl aoetoaoetate in the presence of concentrated sulphuric acid to give 4-methyl-7-hydroxycoumarin. 

Methyl n-amyl carbinol. 247, 254 Methyl n-amyl ketone, 482 Methylaniline (mono), pure, from commercial methylaniline, 562, 570 P-Methylanthraquinone, 728, 740 Methyl benzoate, 780, 781 p-Methyl benzyl alcohol, 811,812 Methyl benzyl ketone, 727, 735 Methyl y-bromocrotonate, 926, 927 2-Methyl-2-butene, 239 Methyl n-butyl carbinol, 247,255 Methyl n-butyl ether, 314 Methyl n-butyl ketone, 475, 481 4-Methylcarbostyril, 855 p-Methylcinnamic acid, 719 4-Methylcoumarin, 853, 854 Methyl crotonate, 926, 927 Methylethylacetic acid, 354, 358 Methylethylethynyl carbinol, 468 Methyl ethyl ketone, 335, 336 purification of, 172 Methyl n-hexyl ether, 314 Methyl n-hexyl ketone, 335, 336 Methyl n-hexyl ketoxime, 348 Methyl hydrogen adipate, 938 Methyl hydrogen sebacate, 938,939 4-Methyl-7-hydroxycoumarin, 834 Methyl iodide, 287 Methyl isopropyl carbinol, 247,255 Methyl 4-keto-octanoate, 936... 

Fig. 5 SIM chromatograms obtained in NI discharge-on TSP/LC-MS of mixed reference standards (5 ppm) (top) and of a spiked (1 ppm) lean beef muscle sample (bottom). Peak identities (1) p-nitrofenol, (2) 3-chloro-4-methyl-7-hydroxycoumarin, (3) 3-methy-4-(methylthio)phenol, (4) paraoxon, (5) couma-phos oxon (6) famphur (7) 2.4,5-trichlorofenol, (8) ronnel oxon, (9) stirofos, (10) parathion, (11) cou-maphos, (12) chlorpyriphos-methyl, (13) ronnel, (14) chlcpyriphos. (From Ref. 75.)...

Polyhydric phenols, particularly when the two hydroxyl groups are meta oriented, react with great ease. If sulphuric acid is used as the condensing agent, careful temperature control is needed to ensure a good yield (e.g. 4-methyl-7-hydroxycoumarin, cognate preparation in Expt 8.45). In these cases the use of polyphosphoric acid is recommended and this alternative process is illustrated. Good yields are also obtained from polyhydric phenols by condensation in the presence of trifluoroacetic acid.30... 

Resorcin reacted with 3-oxo-butyric acid ethyl ester in the presence sulfuric acid and phosphorous pentaoxide and 4-methyl-7-hydroxycoumarine (hymecromone) was obtained. 

Coumarins are an important family of fragrance chemicals with herbaceous, haylike odors. The conventional methods for coumarin synthesis require drastic conditions. For example, 4-methyl-7-hydroxycoumarin 39 (Eq. 15.4.1) is prepared via the Pechmann reaction by stirring a mixture of resorcinol 37 and ethyl acetoacetate 38 in H2SO4 for 12-14 h (63). 

CHLORO-4-METHYL-7-HYDROXYCOUMARIN DIETHYL THIOPHOSPHORIC ACID ESTER see CNU750... 

Haloxon (20a) is prepared by treating 3-chloro-4-methyl-7-hydroxycoumarin (53) with 0,0-di(2-chloroethyl)phosphoryl chloride [56], while coumafos (20b) is obtained by condensing 53 with 0,0-diethylthiophosphoryl chloride in the presence of potassium carbonate and copper powder at 50-100 C [57,58]. 

Chloro-4-methyl-7-hydroxycoumarin Diethyl Thiophosphoric Acid Ester 3-Chloro-7-hydroxy-4-methyl-coumarin 0,0-Diethyl Phosphorothioate 3-Chloroisobutene 3-Chloroisobutylene 3-Cloro-2-metil-prop-l-ene 3-Dimethylamionpropyl N,N-Dimethyl-phosphoramidofluoridate 3-[(Dimethoxyphosphinyl)oxy]-2-butenoic Acid Methyl Ester... 

---