Hydroxy-2-methylpyran

Hydroxy-2-methylpyran-4-one (427), maltol, is an important flavouring agent and some consideration has been paid to its synthesis. A number of routes have been developed... 

Both the hetero and carbonyl oxygen atoms of maltol, 3-hydroxy-2-methylpyran-4-one, are replaced by sulfur on treatment with Lawesson s reagent. While the ketone —> thione conversion can be achieved with various sulfur reagents, the heteroatom exchange is unusual and appears specific for Lawesson s reagent (Equation 179). This reaction does not occur with either related chromones or xanthones <2006CC206>. 

In acid-based reactions 2-acetyl-3-hydroxyfuran (isomaltol) (5.76), 3-hydroxy-2-methylpyran-4-one (5.77), and maltol (5.79) are formed. They are responsible for the baked bread aroma. 

Pyrans occurring in foods are hypothetically derived from a-pyran or y-pyran, or from a- or y-pyrones, respectively. 8-Lactones can also be considered derivatives of a-pyran. An important a-pyrone is 3-hydroxypyran-2-one, also known as 3-hydroxy-2-pyrone or 3-hydroxy-2ff-pyran-2-one, which is a 8-lactone of 2,5-dihydroxypenta-2,4-dienoic acid with a caramel-Hke flavour, which arises from ascorbic acid (see Section 5.14.6.2.2). Undoubtedly, the most important y-pyrone is 3-hydroxy-2-methylpyran-4-one, which is known as maltol (8-167), featuring a caramel (or malt) smell and taste. A large number of other y-pyrones are formed in non-enzymatic browning reactions, but as flavourings they are of Httle consequence. 

As a first step in the prepartion of polymers patterned after the repeating unit of nonactin 56, Moore and Kelley53 synthesized 3,8-dioxabicyclo[3.2.1 ]octan-2-one 57 and its corresponding polyester 58. The monomer was prepared from 5-hydroxy-methylpyran-2-carboxylic acid in overall yield of 20%. It was heated with a catalytic amount of tert-butoxytitanate under nitrogen for 3 hr at 100 °C. The temperature... 

The construction of the furan ring in a Feist-Benary type reaction starting from 4-hydroxy-6-methylpyran-2-one (66) has also proved to be useful for the synthesis of furo[3,2-c]pyridines (Scheme 14) (75JHC461, cf. 71BSF4041). Quite recently the synthesis of the hitherto unknown furo[3,2-c]pyridin-3-ols has been described (79LA371). 4-Hydroxypyridine-3-carboxylates (e.g. 69), which are available from diketene and /3-aminocrotonic esters, react with a-halogenoketones in the presence of potassium carbonate to give compounds of type 70. 

By analogy with the preparation of furo[3,2-c]pyridones (Scheme 14), treatment of 4-hydroxy-6-methylpyran-2-one (66) with chloroacetaldehyde in basic aqueous medium... 

The self-condensation of 1,3-dicarbonyl compounds provides a useful route to 4-hydroxy-pyran-2-ones and is catalyzed by acids or bases. Alcohol is continuously removed during the reaction. Amongst a number of examples, mention can be made of the detailed procedure for the synthesis of 3-acetyl-4-hydroxy-6-methylpyran-2-one (dehydroacetic acid) (550SC(3)23l) and the formation of the cyclopentyl derivative (321) (64RTC39). Deacylation at C-3 can generally be achieved on heating with acid. 

The products of the reaction of 4-hydroxy-6-methylpyran-2-one with alkynic esters show some dependence on the solvent used. Dimethyl butyndioate yields the bicyclic pyranone (325) in the absence of solvent and using Triton B as the catalyst. Michael addition is envisaged to yield the intermediate dione (324) which cyclizes in the normal manner... 

In an extension to the above methodology, a sequential 1,2-addition, dehydration, and in situ ring closure via a 67t-electron electrocyclic cyclization has been described in the context of the pharmacologically relevant natural products warfarin A, the arisugacins, merulidial, and isovelleral (Scheme 20) <2005CAR1287>. Carbohydrate-derived a,3-unsaturated enals were coupled with 4-hydroxycoumarin 188 and 4-hydroxy-6-methylpyran-2//-one 191 in the presence of proline catalysts to provide pyrone-annulated products of types 190 and 192. Stereoselective electrocyclic ring closure was observed only when hydroxyl functionality (at any of R -k ) on the enal was acyl protected. 

In the presence of acetic acid and pyridine, 5-phenyl- or 5- eri-butyl-3-methylthio-l,2-dithiolium ions have been reacted with cyanoacetone to give, in the usual way, an a-(l,2-dithiol-3-ylidene) ketone. A similar reaction has been observed with 4-hydroxy-6-methylpyran-2-one and with 4-hydroxy-coumarin (Eq. 23). In the same way, 4-hydroxy-6-methylchromene-2-thione and 3-methylthio-5-phenyl-l,2-dithiolium cation gave the fused trithiapentalene 59. ... 

Lutidones rather than 4-hydroxy-2-pyridones are formed from dehydroacetic acid (XII-235) and ammonia or primary amines. With one equivalent of aqueous or ethanolic primary amine at ambient temperatures, dehydroacetic acid gives 3-(a-alkylaminoethylidene)-6-methylpyran-2,4-diones (XI-236). An excess of amine (R = Me, Et, n-Pr, n-Bu, CH2C6H5, CH2CH2CjHs) and dehydroacetic acid give 2,6-bisaIkylaminohepta-2,5-dien-4-ones (XII-237) or the lutidones (XU-238), depending on conditions. Aqueous ammonia... 

ZaR AR, lS,%aR -Tetrahydro-7-hydroxy-2,2-dimethyl-4,7-methano-l, 3-dioxolo[4,5-c]oxepin-6(4//)-one, Q-10 Tetrahydro-3-hydroxy-5-hydroxymethyl-3-furancarboxylic acid, T-26 2,3,3a, 9a-Tetrahydro-3-hydroxy-6-imino-6/ -furo[2, 3 4,5]oxazolo[3,2-a]-pyrimidine-2-methanol, C-170 Tetrahydro-5-hydroxy-3-methylene-2-furanmethanol, D-629 7,8,9,10-Tetrahydro-8-hydroxy-3-methyl-6,9-epoxy-2ff,6ff-pyrimido[2,l-6]-[l,3]oxazocin-2-one, A-715 Tetrahydro-2-hydroxy-6-methylpyran, H-144 Tetrahydro-2-(hydroxymethyl)pyran, T- ... 

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