HAFNER Azulene Synthesis

The 4-methyl group of the azulenes (752) condense slowly as mentioned with (7) to give the red azulene-4-dieneamines (755). The latter are related to the dieneamino-fulvene (7) of the classical Hafner-azulene synthesis, and on heating afford in a (jrlOj)-ring-closure the cyclopenta(e,f)heptalenes (154)18> 72 rather than the benz(e)azulenes in a ( 6s)-cyclization. 

In the Hafner azulene synthesis, pyrylium salts are subjected to cyclocondensation with cyclopentadienyl anions thus 4,6,8-trimethylazulene (50) is obtained from 2,4,6-trimethyl pyrylium salts and Na-cyclopentadienide via intermediates 48/49 (cf also p. 379). 

Pyridinium ions with acceptor substituents, for example, N-(2,4-dinitrophenyl) pyridinium salts 231 (cf p. 356), are converted to pentamethine cyanines 232 (Konig s salts) by ring-opening with secondary amines. Cyanines 232 condense with Na-cyclopentadienide to yield vinylogous aminofulvenes 233, which on cyclization afford azulene (Ziegler/Hafner azulene synthesis, cf p. 304) [137] ... 

Fulvene derivatives can serve as building blocks for construction of the polycyclic conjugated systems. Polycyclic conjugated systems involving a fulvene moiety such as azulene 4, pentalene 5, and indacene 6 have also received much attention from the viewpoint of aromaticity (Figure 6.2), and their synthesis has been developed on the basis of fulvene chemistry. In the well-known Ziegler-Hafner azulene synthesis, a fulvene derivative 7 is employed as an important intermediate (Scheme 6.1) [2]. 

During the 1950s and 1960s Hafner used Konig salts, derived from the reaction of A -methyl aniline with Zincke salt 1, for azulene synthesis. The Zincke reaction also achieved prominence in cyanine dye synthesis and as an analytical method for nicotinamide determination. ... 

Hafner s synthesis of azulene,216 the cyclopentadienyl anion can also be used to introduce the five-membered fragment. This anion reacts with heterocyclic quaternary salts in a complex manner the pseudoazulene, however, is obtained in one step. The total yields are only about 10%, but it is possible to use starting materials that are easily available in large quantities. This variant was applied to prepare 2H-cyclopenta[thiadiazolium salts145 and cyclopenta[c]thiopyranes (31) using N-methyl thiazoliumbromide.90... 

Ring fission of pyridinium ions with acceptor substituents, e.g. 7V-2,4-dinitrophenylpyridinium salts 221 (see p 280) leads, on treatment with secondary amines, to pentamethine cyanines 222 (Konig s salts). They condense with sodium cyclopentadienide to yield vinylogous aminofulvenes 223, which on cyclization produce azulene (azulene synthesis according to Ziegler and Hafner, see p 229 [73]) ... 

Pyridazines. Hafner et al. (78H(11)387) used variants of their azulene synthesis to construct azuleno[8,l-cd]pyridazines by... 

Azulene oligomers and polymers are intriguing molecules in terms of tiie construction of functional substances. Some synthetic studies on azulene dimers have been reported. The synthetic methods, however, were considered to restrict the development of further studies. Thus, Ullman coupling reactions at high temperature or some sophisticated reactions based on Hafner s azulene synthesis, starting from bipyridyls, were used. To obtain azulene oligomers, the Suzuki coupling has been applied recently (Equations 10 and 11) [llj. 

Of the fundamental nonalternant hydrocarbons, only two prototypes were known about fifteen years ago azulene (XI, Fig. 5), the molecular structure of which was determined by Pfau and Plattner and fulvene (XIX) synthesized by Thiec and Wiemann. Early in the 1960 s many other interesting prototypes have come to be synthesized. Doering succeeded in synthesizing heptafulvene (XX) fulvalene (XXI) and heptafulvalene (XXIII). Prinzbach and Rosswog reported the synthesis of sesquifulvalene (XXII). Preparation of a condensed bicyclic nonalternant hydrocarbon, heptalene (VII), was reported by Dauben and Bertelli . On the other hand, its 5-membered analogue, pentalene (I), has remained, up to the present, unvanquished to many attempts made by synthetic chemists. Very recently, de Mayo and his associates have succeeded in synthesizing its closest derivative, 1-methylpentalene. It is added in this connection that dimethyl derivatives of condensed tricyclic nonaltemant hydrocarbons composed of 5- and 7-membered rings (XIV and XV), known as Hafner s hydrocarbons, were synthesized by Hafner and Schneider already in 1958. 

A prototype for the new cyclization reaction is the Ziegler-Hafner synthesis of azulene (J)4 by heating the fulvenoid decapentaene (/). Woodward28 was the first to argue that a thermal, electrocyclic [rr 10 s] ring-closure could be involved in this thermolytic process. Of course it seems likely that the nonisolable intermediate (2) may be formed by an intramolecular electrophilic attack of atom 10 to the electron-rich position 1 in compound (1). Indeed a distinction between the two different reaction modes is mechanistically irrelevant in this case. But only its interpretation as an electrocyclic process allows the generalization to [ir 6 s] cyclizations too. 

The formation of azulenes by cyclocondensation of cyclopentadienyl anions is a prime example of a synthesis with pyrylium salts (Hafner 1973 [8], cf 307). Thus, 4,6,8-trimethylazulene 46 is produced by the reaction between 2,4,6-trimethylpyrylium salts and sodium cyclopentadienide, resulting in ring-opening at C-2 (45) followed by ring closure of the cyclopentadienyl system 47 which is a probable intermediate. 

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