Ciamician-Dennstedt rearrangement

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.  

It has been suggested that the strain of the [3.1.0] ring system plays a role in facilitating the reaction. In a carbocyclic system, the [3.1.0] ring system opens 200 times faster than the analogous [4.1.0] ring system.  

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.  

Flash vapor pyrolysis of chloroform has been used to effect the 

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

---

The rearrangement of pyrroles to 3-halo-pyridines upon treatment with haloforms (CHX3 where X = Cl, Br, I) in the presence of a strong base was first described by G.L. Ciamician. Its synthetic utility was later extended by M. Dennstedt to the sodium methoxide catalyzed reaction of pyrrole with methylene iodide to give pyridine. Soon after the initial discovery, the methodology was also extended for the indole series to prepare substituted quinolines. The reaction is known as the Ciamician-Dennstedt rearrangement, but it is also referred to as the abnormal Relmer-Tiemann reaction. 

Ciamician-Dennstedt rearrangement Synthesis of 3-halopyridines from pyrroles and 2-haloquinolines from indoles. 84... 

Ciamician-Dennstedt rearrangement. Expansion of the pyrrole ring by heating with chloroform or other halogeno compounds in the alkaline solution. The intermediate dichlorocarbene, by addition to the pyrrole, forms an unstable dihalogeno-cyclopropane that rearranges to a 3-halogenopyri-dine. 

Ciamician-Dennstedt Rearrangement Claisen (see Darzens-Claisen Reaction)... 

---