Coumalic acid

Coumalic acid, decarboxylation of, apparatus for, 46, 102 to give a-pyrone, 46,101 purification of, 46,102 Coumarilic acid, 46, 29 Coumarone, 46, 28... 

Dihydro-2f/-pyran-2-one has been prepared by reductive cycliza-tion of 5-hydroxy-2-pentynoic acid [2-Pentynoic acid, 5-hydroxy-], which is obtained in two steps from acetylene [Ethyne] and ethylene oxide [Oxirane] 3 and by the reaction of dihydropyran [277-Pyran, 3,4-dihydro-] with singlet oxygen [Oxygen, singlet].4,5 2ff-Pyran-2-one has been prepared by pyrolysis of heavy metal salts of coumalic acid [2//-Pyran-5-carboxylic acid, 2-oxo-],8 by pyrolysis of a-pyrone-6-carboxylic acid [211 - Pyran-6-carboxyl ic acid, 2-oxo-] over copper,7 and by pyrolysis of coumalic acid over copper (66-70% yield).8... 

Coumalic acid, 56, 51 Crotyl fluoride, 57,73 18-CROWN-6,57, 30 Curtius rearrangement, 59, 1 Cyanide ion, as catalyst for conjugate addition of aldehydes, 59, 56 p-Cyanobenzenesulfonyl cyanide, 57, 89 2-( 1 -Cyanocyclohexyljhydrazinecarboxylic acid methyl ester, 58,102 Cy a noferrocene, 56, 30 Cyanogen chloride, 57, 88... 

Emulsion, minimizing of, 37, 31 Enanthaldehyde, 34, SI ENANTHALDEHYDE, C-METHYL-/3-OXO-, DIMETHYL ACETAL, 32, 79 Enanthic acid, e-oxo, 31, 3 Epichlorohydrin, 31, 1 Esterification, by azeotropic distillation with toluene, 30, 30, 31 of coumalic acid with methanol, 36, 44 of diethoxyacetic acid, 35, 59 of ethanol with phosphorus trichloride,... 

In the von Pechmann synthesis, originally used to prepare pyran-2-one-5-carboxylic acid (coumalic acid), 2-hydroxybutane-l,4-dioic acid is converted into 3-oxopropanoic acid by treatment with oleum (sulfur trioxide and cone, sulfuric acid), and this product then self-condenses in the acidic medium to give pyran-2-one-5-carboxylic acid (Scheme 4,8a). Pyran-2-one is obtained by decarboxylating coumalic acid by heating it over copper at 650 °C. 

Coumalic acid, 4,6-dimethyl- and coumalic acid, 4,6-dimethyl-,... 

Pent-2-ene-l,5-diones may be formed in situ (usually by an aldol-type reaction) and subsequently cyclized. Thus, malic acid (i.e. hydroxy succinic acid) with sulfuric acid gives carboxy acetaldehyde (155) which cyclizes spontaneously to coumalic acid (156). 

Pyridazinedione (167) readily condenses with butadiene, 2,3-dimethylbutadiene and coumalic acid to give the respective Diels-Alder adducts (168). 

Another pathway which is often used in the preparation of this ring system involves the Diels-Alder reaction. 3,6-Pyridazinedione (139) is known to be exceptionally reactive toward dienes. This dienophile readily condenses with butadiene, 2,3-dimethylbutadiene and coumalic acid to give the respective Diels-Alder adducts (140). 3,6-Pyridazinedione is also reported to decompose with evolution of nitrogen gas at temperatures below 0 °C, giving the pyridazino[l,2-a]pyridazine-l,4,6,9-tetrone (44) as the major product (62JA966). 

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. 

A 37.5-g. (0.266-mole) sample of coumalic add (Note 1) is placed in a 30 x 10 cm. cylindrical flask attached horizontally to a 55 x 3 cm oven-heated Vycor tube (Note 2) loosely packed with 20 g. of fine copper turnings (Note 3). Following the Vycor tube successively are two ice-cooled 50-ml. receivers and a dry ice trap. The latter is connected to an efficient vacuum pump (Note 4). The system is evacuated, and the Vycor tube is heated to 650— 670° Then the flask containing the coumalic acid is heated with a nichrome wound heating jacket to 180°, and the temperature is allowed to rise slowly to 215°. During this time coumalic acid sublimes into the Vycor tube and a-pyrone distills into the ice-cooled receivers. The pressure is held below 5 mm (Note 5) The yield of pale yellow crude material is 18-19 3 g. (70-75%). 

Better yields are obtained at low pressures (preferably below 5 mm.) because of more efficient sublimation of coumalic acid. The submitters report that a water aspirator could be used with crude (unrecrystallized) coumalic acid to avoid damage to the vacuum pump by untrapped corrosive vapors, and that yields of a-pyrone averaged 45% in this modification. The checkers used a mechanical pump with an efficient sodium hydroxide trap in all runs. 

In this section the synthesis of coumalic acid (92), representing the a(2)-pyrone system, is described. a-Pyrones readily undergo a simple lactone-amide transformation, and the conversion of coumalic acid into the tautomeric 6-hydroxy-nicotinic acid (93) provides a further illustration of the conversion of a six-membered oxygen heterocycle into the corresponding nitrogen system. 

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