Formation of heterocyclic compounds

Miscellaneous reactions in neutral ionic liquids Kitazume et al. have also investigated the use of [EDBU][OTf as a medium in the formation of heterocyclic compounds [58]. Compounds such as 2-hydroxymethylaniline readily condense with... 

Strecker aldehyde are generated by rearrangement, decarboxylation and hydrolysis. Thus the Strecker degradation is the oxidative de-amination and de-carboxylation of an a-amino acid in the presence of a dicarbonyl compound. An aldehyde with one fewer carbon atoms than the original amino acid is produced. The other class of product is an a-aminoketone. These are important as they are intermediates in the formation of heterocyclic compounds such as pyrazines, oxazoles and thiazoles, which are important in flavours. 

Oxidative rearrangements resulting in the formation of heterocyclic compounds are relatively less explored, although some of them are quite important. A basic reaction is the conversion of a chalcone to 3,3-dimethoxy-l-phenylpropanone (Eq. 2) (85TL2961). This process may be adapted to heterocyclic synthesis. 

Such direction with the formation of heterocyclic compounds 123 was also observed for the MCR of 2,4-dioxobutanoates and aldehydes with 5-amino-1-methyl-tetrazole. The authors did not discuss the reasons for different pathways of these MCRs. 

The final important category of [4 + 2] cyclization is the Diels-Alder and other [4 + 2] cycloaddition reactions. This topic has been the subject of intense study for many years and continues to attract the attention of many researchers, as in a great many instances the reactions involved constitute excellent procedures for the synthesis of both heterocyclic and non-heterocyclic compounds. The discussion in this section is restricted to processes which result in the formation of heterocyclic compounds from non-heterocyclic precursors, although of course a heterocycle may be present as a substituent in either the diene or ene component but have no significant or controlling effect in the cycloaddition reaction. 

M.R. Grimmett, Formation of Heterocyclic Compounds from Carbohydrates and Ammonids, Rev. Pure Appl. Chem. 15, 101 108 (1965). 

From Scheme 2, it may be seen that D-glucosylamine and D-fructo-sylamine are also considered to be intermediates in the formation of heterocyclic compounds. This intermediary formation of 1-amino-1-deoxy-D-fructose and D-glucosylamine from D-glucose and am-... 

G. Vernin, Mechanism of Formation of Heterocyclic Compounds in Maillard and Pyrolysis Reactions, Chem. Heterocycl. Compd. Flavours Aromas 1982, 151-207. 

As previously indicated (see pp. 88-91), formation of heterocyclic compounds, mainly pyrazines, was found only in the ammonolysis of some aldose nicotinates33 35 and acetates and benzoates of ketoses.39 37 For ketose esters, whose behavior differed from that of the aldose esters, the formation of imidazole derivatives was also observed these heterocyclic compounds also result from the direct action of ammonia upon the corresponding free sugars, but the presence of the esterifying acyl groups evidently increases their ease of formation and raises their yields. 

A useful property of hyper valent iodine reagents is their ability to react first as an electrophile and then to be transformed into an excellent leaving group. This particular aspect has been used in different rearrangements for the construction of highly functionalized molecules. Various iodine(III) reagents have been employed in Hofmann-type rearrangements [136-139]. The presence of a nucleophile in the ortho position of aromatic amides of type 72 can lead to direct cyclizations and to the formation of heterocyclic compounds 73 as shown in Scheme 33 [140]. 

Scheme I. Formation of heterocyclic compounds in food products. (Reprinted with permission from ret 4. Copyright 1982 Ellis Horwood Limited.)...

Contribution of Lipids to the Formation of Heterocyclic Compounds in Model Systems... 

The majority of heterocyclic compounds are formed through thermal interactions of reducing sugars and amino acids, known as Maillard reactions. Other thermal reactions such as hydrolytic and pyrolytic degradation of food components (e.g. sugars, amino acids and vitamins) and the oxidation of lipids also contribute to the formation of heterocyclic compounds responsible for the complex flavor of many foodstuffs. 

Recent studies in our laboratory show that lipids may be directly associated with the Maillard reaction in the formation of some heterocyclic compounds. The effect of lipids on the formation of heterocyclic compounds in a model Maillard reaction has also been reported by Mottram and Whitfield (2). 

According to the formation mechanism of heterocyclic compounds from a model system of aldehydes, hydrogen sulfide and ammonia (11), aldehydes such as acetaldehyde and hexanal must have been involved in the formation of heterocyclic compounds identified in this study. 

The a-aminoketones are important for the formation of heterocyclic compounds via condensations with the reductones or with themselves. The aldehydes mentioned, and the heterocyclic compounds are the actual flavour components. 

Of the different types of lipids in foods, the phospholipids, being more unsaturated, are particularly important in relation to aroma formation in meat.151 The aroma of cooked meat was not affected by the prior extraction of triglycerides with hexane, but the use of a more polar solvent (chloroform-methanol), which extracts all lipids, including phospholipids, resulted, after cooking, in the replacement of the meaty aroma by a roast or biscuit-like one. This was reflected in the volatiles, the dominant aliphatic aldehydes and alcohols being replaced by alkylpyrazines. This implies that the participation of the lipids in the Maillard reactions inhibited the formation of heterocyclic compounds. 

G. Vernin and C. Parkanyi, Mechanisms of formation of heterocyclic compounds in Maillard and pyrolysis reactions, in Chemistry of Fleterocyclic Compounds in Flavours and Aromas, G. Vemin (ed), Ellis Horwood, Chichester, 1982, 151-207. 

M. Sakaguchi and T. Shibamoto, Formation of heterocyclic compounds from the reaction of cysteamine and D-glucose, acetaldehyde, or glyoxal, J. Agric. Food Chem., 1978, 26, 1179-1183. 

Electrolytic formation of carbon bonds during formation of heterocyclic compounds occurs in the reduction of ketones to pinacols, in the hydrodimerization reaction, in some radical coupling reactions, and in the oxidative coupling of activated aromatic systems. 

Electrochemical alkylation and acylation are well-established reactions and have been employed for the formation of heterocyclic compounds. The reduction of azobenzene [127] or azomethine compounds [128] in the presence of Q ,ft>-dibromoalkanes leads to cyclic hydrazines, piperazines, or pyrrolidines. Similarly, reduction of nitrobenzene in the presence of 1,5-dibromopentane yields iV-phenylperhydro-l,2-oxazepine [129]. 

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