Glutacon-dialdehyde

Amanita musaaria.- A yellow pigment isolated from the fly agaric mushroom has been identified as the dihydroazepine (34) and its synthesis via a biomimetic route involved the conversion of 3-(2-carboxy-5-pyridyl)alanine to the glutaconic dialdehyde (35) and thence to (34). 

Pyrylium perchlorate 38 forms colourless crystals which are prone to hydrolysis and decompose explosively at 275°C. It can be obtained from A -acceptor substituted pyridinium ions (see p 272), e.g. by the SO3 complex 35, on treatment with NaOH followed by addition of HCIO4. Initially, the orange-coloured sodium salt of 5-hydroxypenta-2,4-dienal (glutaconic dialdehyde in the enol form) 36 is formed which subsequently cyclizes via the red protonated species 37 [7] ... 

If the azine structure is considered by itself, then the retrosynthetic analysis can start at the imine structural element (H2O addition O -> C-2, retrosynthetic path a). Suggestions for the cyclocondensation of various intermediates arise based on the 5-aminopentadienal or -one system 145, and further (path g, NH3 loss) on pent-2-endial (glutaconic dialdehyde) or its corresponding diketone 146. Consideration of a retro-cycloaddition (operation c) leads to the conclusion that a synthesis of pyridines by a cocyclooligomerization of alkynes with nitriles is possible. 

Pent-2-endial (glutaconic dialdehyde) undergoes cyclization with ammonia to give pyridine. It yields pyridine-1-oxide with hydroxylamine and A-substituted pyridinium ions with primary amines. With acids, the pyrylium ion is formed reversibly. Hence pyridine derivatives (see p 230) can also be obtained by reacting pyrylium ions with NH3 and primary amines. 

Dicarbonyl compounds of various types can be used for pyridine formation. For instance, glutaconic dialdehyde (155) undergoes cyclization with NH3, primary amines, or hydroxylamine to give pyridine or pyridine derivatives, for example, ... 

As well as the reactions discussed above, there are recorded several less well defined which probably involve similar processesi208-ii Thus, pyridine, sodium hydroxide and chloroform (and related compounds) quickly produce an intense red colour io. Dichlorocarbene may be involved. Pyridine homologues give isonitriles of the benzene series under these conditionsi n. The pyridine-bisulphite compound mentioned above (p. 249) yields glutacon-dialdehyde dianil with caustic soda and anilinei2i2 ... 

For example, when pyridine reacts in 2,4-dinitrochlorobenzene in an alkaline medium [for review see (115)], leading to a red solution, it is supposed that the corresponding pyridine salt is formed first, which is then cleaved with the formation of 2,4-dinitroanil of glutaconic dialdehyde, the sodium salt of which is red (116). 

The cleavage with cyanogen bromide (117) or chloride (KCN plus chloramine T) (118), or with thionyl chloride, has a similar course. In all instances glutaconic dialdehyde is the cleavage product and it is detected by condensation either with an aromatic amine (see p. 215), for example, aniline, 2-naphthylamine (119) or benzidine, with the formation of dianils, or with compounds with an active methylene group, as, for example, barbituric acid or dimedone with the formation of pentamethine dyes (120, 121). 

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