Dennstedt

CIAMICIAN - DENNSTEDT Cyclopropanation Cyclopropanation of alkenes with dichlorocarbene derived Irom CHCI3 and sometimes subsequent rirtg enlargement of fused cyclopropanes 1 Na... 

In addition to the formation of the pyridine framework by de novo approaches (see section 8.1) or by the cycloaddition/cycloreversion sequence (see section 8.2), one can employ reactions that proceed through a rearrangement pathway. The Boekelheide reaction (see section 8.3.1) involves the rearrangement of an existing pyridine skeleton to a more functionalized scaffold, while the Ciamician-Dennstedt reaction (section 8.3.2) generates the pyridine nucleus by rearrangement of an alternative heterocycle. 

The Ciamician-Dennstedt reaction involves the reaction of a pyrrole (1) with the carbene generated from chloroform and a base to provide a 3-chloropyridine (2, Scheme 8.3.1). 

Ciamician and Dennstedt reacted the potassium salt of pyrrole with chloroform in ether and isolated, after much purification, 3-chloropyridine, which was confirmed by crystallization with platinum. While the pyrrole salt can be used as the base, the chloroform carbene is typically formed with an alkali alcohol. Forty years later, Robinson and co-workers made 3-chloroquinolines from indoles using the Ciamician-Dennstedt reaction. ... 

The Ciamician-Dennstedt reaction can be thought of as the complement to the Reimer-Tiemann reaction (Scheme 8.3.2). The first step of both reactions is cyclopropanation of one of the carbon-carbon double bonds of a pyrrole with a dichlorocarbene, resulting in intermediate 3. The Ciamician-Dennstedt reaction results from cleavage of the internal C-C bond and elimination of chloride (path a), while the Reimer-Tiemann reaction results from cleavage of the exocyclic bond, and subsequent hydrolysis of the dichloromethyl moiety to furnish aldehyde 5 (path b). 

The highest yields in the Ciamician-Dennstedt reaction have been achieved using phase transfer catalysts (Table 8.3.1). In the reaction, the pyrrole or indole and a phase transfer catalyst (PTC, in this case benzyltriethylammonium chloride) are dissolved in chloroform and aqueous sodium hydroxide is added. Yields are typically in the 40s to 60s (rather than in the 20s for a typical Ciamician-Dennstedt reaction). More recently, yields as high as 80% have been reported using tetra-n-butylammonium hydrogen sulphate as the phase transfer catalyst. ... 

Table 8.3.1. Comparison of Phase Transfer Catalysts on Yield of Ciamician-Dennstedt reaction...

The use of sodium tribromoacetate as the dibromocarbene precursor has been investigated and found to provide the Ciamician-Dennstedt product in higher yield than the traditional alkoxide/alcohol reaction conditions. Deprotonation of bromoform with sodium ethoxide in ethanol and reaction of the resultant carbene with 6 provides quinoline 9 in 9% yield thermolysis of sodium tribromoacetate in the presence of 6 furnishes 9 in 20% yield (Scheme 8.3.3). 

Ciamician-Dennstedt reaction on pyrrole, as well as pyrazoles, indoles, and Phenyl(trichloromethyl)mercury has been used as a dichlorocarbene... 

The Ciamician-Dennstedt reaction has been used to prepare macrocycles. Reaction of 2,3-alkyl linked indole derivatives 10, 11, 13, and 15 with phenyl(trichloromethyl)-... 

The Ciamician-Dennstedt reaction is currently the only way to date to make calix[4]pyridine 20.(Scheme 8.3.6) Four sequential treatments of calix[4]pyrrole 19 with sodium trichloroacetate results in all four possible geometric isomers of 20 (all four... 

Though beyond the scope of this book, the carbocyclic analog of the Ciamician—Dennstedt reaction has been investigated. ... 

Connect a wide (3 5-4 cm.) hard glass tube, e.g. a tube used for combustions by Dennstedt s method, by means of a cork with a wide-... 

A dark-brown, amorphous powder, insoluble in water, used for ultimate organic analysis according to Dennstedt. ... 

Angeli35 obtained a white precipitate of insoluble silver azide by mixing saturated solutions of silver nitrite and hydrazine sulfate and allowing to stand in the cold for a short time. Dennstedt and Gohlich 36 later procured free hydrazoic acid by the interaction of hydrazine sulfate and potassium nitrite in aqueous solution. 

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