A-Pyrone-6-carboxylic acid

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... 

DIMETHYL-4-OXO-2H-PYRAN-6-CARBOXYLIC ACID n-BUTYLMESITYLOXID OXALATE 2-CARBO-n-BUTOXY-6,6-DIMETHYL-5,6-DIHYDRO-l,4-PYRONE 3,4-DIHYDRO-2,2-DIMETHYL-4-OXO-2H-PYRAN-6-CARBOXYLIC ACID-n-BUTYL ESTER DIHDYROPYR-ONE 0,a-DIMETHYUa -CARBOBUTOXY-DIHYDRO-7-PYRONE 2,2-DIMETHYL-6-CARBOBUTOXY-2,3-DIHYDRO-4-PYRONE ENT 9 INDALONE... 

A soln. of 3-benzyI-4-hydroxy-6-methyl-2-pyrone-5-carboxylic acid in nitrobenzene treated with 2-3 drops of quinoline and refluxed 15-20 min. 3-benzyl-4-hydroxy-6-methyl-2-pyrone. Y over 90%. F. e. s. K.-H. Boltze and K. Heiden-bluth, B.91, 2849 (1958). 

The cumulation reactions, which start from carboxylic acids and esters usually lead to the formation of pyrone derivatives. Methyl (Z)-3-iodoacrylate and 3-hexyne gave, for example, 5,6-diethyl-2-pyrone in acceptable yield (4.38.). Inclusion of the acrylate into a six membered ring starting from ethyl 2-bromocyclohexen-l-carboxylate, led to a condensed ring system, giving a partially reduced isocoumarin derivative.50... 

Alkynes are easily carboxylated by C02 and usually offer lactones or pyrones as products. However, in several cases carboxylic acids can also be obtained. For example, 2-butyne reacted with C02 in the presence of a [Ni(CDT)] (CDT = 1,5,9-cyclododecatriene) catalyst and /V,/V,/V, /V -tetramethyl-l,2-diamine (TMEDA) as base to yield 2-methylcrotonic acid.21 Similarly, the reaction of terminal alkynes was catalyzed by Ni(COD) in a highly regio- and chemoselective manner in the presence of DBU as base affording E-acrylic acids in >85% yield (Scheme 6.13).84... 

Irradiation of 4,6-dimethyl-a-pyrone immobilized in a guanidinium-sulfonate-calixarene gives rise to a 4,6-dimethyl-Dewar-p-lactone, a carboxyl zwitterion and 1,3-dimethylcyclobutadiene, both in the solid crystalline state and in aqueous solution. Diarylmethyl carbocations have been generated within the cavities of non-protic zeolites (LiY, NaY, KY, RbY, CsY, and NaX) via laser-mediated decarboxylation of diarylacetic acids. 

Related to this methodology is another one recently developed by Kirsch et al. [61], in which (Z)-aUylic alcohols are first converted into their trichloroacetimidates, and the latter are then subjected to a catalytic Sj 2 substitution of the trichloroace-timidate by a carboxylate group under the influence of complex 132, available in both enantiomeric forms (Scheme 2.26). If a p,y-unsaturated acid is used, an allyl P,y-unsaturated ester is obtained, which, after RCM and base-catalyzed migration of the double bond, affords a 5,6-dihydro-a-pyrone. The authors demonstrated the practical applicabihty of this methodology with the synthesis of (-)-rugulactone and other natural products. 

Industrially, a selectivity to DAA of between 90—95% can be achieved (64). The principal by-products are mesityl oxide and acetone trimers. j W-Triacetone dialcohol [3682-91-5] can form by condensation of acetone with diacetone alcohol (116). Dehydration of ry/ -triacetone dialcohol can yield semiphorone [5857-71-6] (6-hydroxy-2,6-dimethyl-2-hepten-4-one), which may in turn ring close to form 2,2,6,6-tetramethyl-y-pyrone [1197-66-6/, or ultimately dehydrate to phorone [504-20-1] (2,6-dimethyl-2,5-heptadien-4-one) (146). Similarly, an unsymmetrical acetone trimer can also be formed which dehydrates to 2,4-dimethyl-2,4-heptadiene-6-one. These impurities complicate the high purity recovery of DAA, and are thought to be responsible for a yellow discoloration of DAA. The addition of dibasic acid (147) or nitrogen containing carboxylic or phosphonic acids (148) has been patented as refined product stabilizing agents. 

Even on prolonged hydrogenation under these conditions, only 23 per cent of the product was the 2,3-dihydro compound. When Raney nickel (p. 90) or platinum oxide [159] is present, reduction of the double bond at the 2,3-positions frequently occurs. When ethyl 6-chlorochromone-2-carboxylate was reduced with zinc dust and acetic acid, a dimeric chromanone was obtained [25a]. Hydrogenolysis of the chlorine and reduction of the pyrone ring occurred with hydrogen and palladium-charcoal [25a]. 

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