5.5- Dimethyl-3- -furanone formation

Naim, M., S. Wainish, U. Zehavi, H. Peleg, R.L. Rouseff, S. Nagy, Inhibition by thiol compounds of off-flavor formation in stored orange juice. I. Effect of L-cysteine and N-acetyl-L-cysteine on 2,5-dimethyl-4-hydroxy-3(2H)-furanone formation, J. Agric. Food Chem., 41(9), p. 1355, 1993. 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Reduction of 3,5,5-tris-aryl-2(5// )-furanones 115 (R, R, R = aryl) with dimethyl sulfide-borane led to the formation of the 2,5-dihydrofurans 116 in high yields. However, in the case of 3,4-diaryl-2(5//)-furanones 115 (R, R = aryl R = H or r = H R, R = aryl), the reduction led to a complicated mixture of products of which only the diarylfurans 117 could be characterized (Scheme 36) (88S68). It was concluded that the smooth conversion of the tris-aryl-2(5//)-furanones to the corresponding furan derivatives with the dimethylsulfide-borane complex in high yields could be due to the presence of bulky aryl substituents which prevent addition reaction across the double bond (88S68). 

The bromination and hydrolysis of ketenes and bisketenes have been studied. The reaction of the bis(ketene) 289 with bromine has yielded the dibromo fumarate derivative 290, whose /r/mr-con figuration has been confirmed by X-ray crystallography (Scheme 41).366 The hydrolysis of the dibromo fumarate derivative 291 first provided the dibromo derivative (5//)-furanone 292. The prolonged reaction with water afforded the maleic anhydride 293. The methanolysis of the dibromo fumarate derivative 290 has resulted in the formation of an isomeric mixture of dimethyl... 

Scheme 13.14 Formation of 4-hydroxy-2,5-dimethyl-(2H)-furanone from rhamnose...

The reaction of a-bromoacetals with trimethylsilylenolates catalyzed by titanium tetrachloride provides /3-alkoxy-y-bromoketones, which are useful furan precursors (Scheme 33) (75CL527). A new synthesis of acylfurans is exemplified by the formation of the 3-acetyl derivative (146) by heating the brdmoalkene (145) (78JOC4596). 2,2-Dimethyl-3(2//)-furanone (148) has been synthesized from 3-hydroxy-3-methylbutan-2-one treatment with sodium hydride and ethyl formate gave the hydroxymethylene derivative (147), which was cyclized and dehydrated to the furanone (148) with hydrochloric acid (Scheme 34) (71TL4891). O... 

Blank, I., Lin, J., Fumeaux, R., Welti, D.H., and Fay, L.B. 1996. Formation of 3-hydroxy-4,5-di-methyl-2(5H)-furanone (sotolone) from 4-hy-droxy-L-isoleucine and 3-amino-4,5-dimethyl-3,4-dihydro-2(5)-furanone. J. Agric. Food Chem. 44 1851-1856. 

FIGURE 7.11 Formation of Sotolon (3-hydroxy-4,5-dimethyl-2(5H)-furanone) in wines by aldol condensation of acetaldehyde and 2-oxobutanoic acid followed by lactoni-zation (Kobayashi, 1989). 

A maltol-ammonia browning reaction produced thirteen pyrazines, two pyrroles, two oxazoles, and one pyridine (12). The major products of this system were 2-ethyl-3-hydroxy-6-methylpyridine and 2-ethyl-3,6-dimethylpyrazine. It is difficult to construct possible formation mechanisms for these compounds from maltol and ammonia. All the carbon atoms must come from maltol. It is possible, then, that maltol degrades into smaller carbon units and that these fragments recombine to form larger carbon units, producing these compounds. Recently, the formation of thiophenones and thiophenes from the reaction of 2,5-dimethyl-4-hydroxy-3(2H)-furanone and cysteine or cystine was reported (13. 14). All these reaction mixtures were reported to possess a cooked meat-like flavor. 

Dimethoxy Phenol 3,4-Dimethyl 1,2-Cyclopen tandione 5-Ethyl 3-Hydroxy 4-Methyl 2(5H)-Furanone 3-Ethyl Pyridine Furfuryl Mercaptan Geranyl Isovalerate 2,3 -Heptandione (Z)-3-Hexenyl Butyrate (Z)-3-Hexenyl Formate Hexyl Butyrate Hexyl Hexanoate Isoamyl Isobutyrate Isobutyl Formate Isobutyl Hexanoate Linalool Oxide... 

Fig. 3.26 Formation of4-hydroxy-2,5-dimethyl-3(2H)-furanone from 1-deoxyhexosone 3.2.3.3.2 Lipid Oxidation...

Blank, I., Fay, L.B. Formation of 4-hydroxy-2,5-dimethyl-3(2//)-furanone and 4-hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2//)-furanone through MaiUard reaction based on pentose sugars. J. Agric. Food Chem. 1996, 44, 531-536. 

Me) at 180°C led to a 7 1 mixture of 4,4-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one (19) and 4,5,5-trimethylfuran-2(5//)-one (20). ° The formation of product 19 can be rationalized by intramolecular addition of the carboxy group across the exocyclic C — C double bond, whereas furanone 20 is probably the result of an intramolecular trapping of the diradical intermediate of the methylenecyclopropane rearrangement. This assumption was confirmed by pyrolysis of the isomeric add, 2,2-dimethyl-3-methylenecyclopropanecarboxylic acid (18, R = Me R = H), which led to the same products, but in a different ratio (2 7). ... 

In addition, other work showed that 3-hydroxy-4,5-dimethyl-2(5H)-furanone can be formed thanks to a Maillard reaction of hexoses and pentoses in the presence of cysteine 20). Due to the non-linear structure of Sotolon, its formation cannot simply be explained directly from sugar cyclization during tire Maillard reaction, like other furanones such as Furaneol. Hence, it is likely tliat Sotolon results from rearrangement of Amadori products of low molecular weight like butan-2,3-dione (diacetyl) and hydroxyacetaldehyde, via an aldol condensation (Figure 6). 

In continuation of our efforts in the development of new synthetic routes for the synthesis of heterocyclic compounds using nanocatalysts, we have recently reported a novel synthesis of 3,4,5-trisubstituted furan-2(5H)-one derivatives by the one-pot three-component condensation of aldehydes, amines, and dimethyl acetylenedicar-boxylate (DMAD) by nsing nanoparticulate ZnO as a catalyst in Et0H H20 (1 1) at 90°C (Scheme 9.30) (Tekale et al. 2013). Almost all the employed aldehydes and amines reacted smoothly to afford excellent yields of the prodncts, irrespective of the natnre of the snbstitnent present on the aldehyde or amine. The plausible mechanism for the synthesis of furan-2(5 f)-ones using nano-ZnO is depicted in Figure 9.3. The catalyst promotes the formation of enamines (99) from amines (97) and DMAD (96). ZnO polarizes the carbonyl group of aldehydes to form a polarized adduct (100) which reacts with the enamines, followed by cyclization with the elimination of methanol molecules to afford the corresponding trisubstituted furanone derivatives (98). 

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