Formation of heterocyclic compound from

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). 

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. 

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-... 

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. 

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

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. 

Figure 11.4. Structures of various heterocyclic amines. IQ is 2-amino-3-methylimidazo-quinoline. MelQx is 2-amino-3,8-dimethylLtnidazo-quinoxalme. 4,8-DiMelQx is 2-amino-3,4,8-trimethylimidazo-quinoxaline. PhIP is 2-amino-l-methyl-6-phenylimidazo-pyridine. These and other related compounds can be found in fried or broil beef, fish, and chicken, but can also be created by cooking mixtures of creatinine, amino acids, and glucose. Microwave cooking, or cooking in aluminum foil, reduces the formation of heterocyclic amines. (From Sugimura, 1997.)...

Naturally Occurring Thiophens. - A review on the formation of heterocyclic compounds, including thiophen derivatives, by enzymic and non-enzymic browning in relation to food flavour has been published.Some thiophens have been found as trace constituents in the essential oil from Thymus capitatus " From steam-distilled hop oils, 3-(4-methylpent-3-enyl)thiophen... 

A commercially available polystyryldiphenylphosphine has been used to convert 3 -azido-3 -deoxy-nucleosides into the corresponding 3 -amino-3 deoxy-nucleosides, by formation and hydrolysis of phosphine imine intermediates. The formation of heterocyclic compounds on photolysis of glycosyl azides is covered in Section 6, and the formation of unsaturated sugars by radical elimination of vicinal phenyl selenide and xanthate azides from i ropriate saturated compounds is covered in Chapter 13. 

The structures of chalcogen-nitrogen compounds are frequently unpredictable. For example, the reactions of heterocyclic systems often result in substantial reorganization of their structural frameworks, e.g. ring expansion or contraction. The formation of acyclic products from ring systems (or vice versa) is also observed. 

Identification of the product(s) resulting from the reaction of heterocyclic compounds with diazomethane has been used in attempts to elucidate their tautomeric composition (for summaries, see references 7 and 41). This work was based on the assumption that if a compound which is capable of existing in both an —NH and an —OH form produced only the =NMe derivative when it w as treated with diazomethane, it existed entirely in the =NH form. On the other hand, formation of the —OMe derivative was interpreted to mean that a finite amount of the compound existed in the —OH form. In some cases the tautomer present in the solid state w as concluded to be different from that present in solution for example, 41 42 gave a higher proportion of the 3,4-dimethoxy derivative when ethereal diaz-... 

The formation of quaternary salts from benzyl halides and related compounds occurs readily and has been known for many years. More recently, Krohnke and co-workers, who have studied the reactions of many heterocyclic quaternary salts, reported the formation of 5 from pyridine and benzylidene dibromide on heating the reactants together for 1 hr at 100°. The salt is sufficiently stable to be recrystallized from methanol containing a trace of hydrogen bromide. Isoquinoline gives a similar salt. 

A useful route to 2,1,3-benzothiadiazoles is the F -catalyzed cyclization of l-(4-X-C6F4)-3-trimethylsilyl-l, 3-diaza-2-thiallenes [90JFC(50)359]. Fluoride ion catalysis is also used in the formation of heterocycles from pentafluorobenzoyl and -phenoxy compounds (81BCJ3447). Pentafluoro-phenylcarbonimidoyl dichloride with primary amines gave guanidines,... 

Recently, much attention has been paid to hetero Diels-Alder reactions as powerful tools for the construction of heterocyclic compounds. For example, cycloaddition of 2,3-dimethylbuta-l,3-diene 41a with 1,2-thiazinylium salt 95, in acetonitrile at room temperature, resulted in the exclusive formation of product 76a resulting from cycloaddition across the C—S1 bond (see entry 1 in Table 15 and Equation 26) <1999TL1505>. Similarly, isoprene 41b and... 

In the case of the most reactive compounds, substitution at the carbon atom of diselenonium and ditelluronium dications is also a possible pathway. For example, formation of diselenide 117 from selenoxide 115 was explained by demethylation of intermediate dication 116 with trifluoroacetate anion.126 Dealkylation of salt 118, which is stable up to —20°C, leads to formation of nitrilium salt 119. The latter is transformed to amide 120 upon hydrolysis.64 Dealkylation of intermediate diselenonium dication 122 was suggested as the key step in the oxidative synthesis of 1,2,4-diselenazolidines 123 from eight-membered heterocycles 121 (Scheme 46).127... 

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