Dimroth reaction

In the reactions described in Section III,C, a three-atom fragment in the heterocycle is replaced by the same atoms of the reagent and with the same sequence of atoms. This type of reaction has been referred to as an inter-molecular transfragment reaction (67JA6911) and therefore can be clearly distinguished from molecular rearrangements, such as the Dimroth reactions (68MI1 see also Chapter IV) and photochemical transposition reactions. 

As in the case of 2,2 -bipyridine, the most important synthetic routes to 4,4 -bipyridine use pyridine as starting material. One method of synthesizing 4,4 -bipyridine from pyridine was discovered by Dimroth in 1921. If pyridine in acetic anhydride is treated with zinc dust, l,l -diacetyl-l,r,4,4 -tetrahydro-4,4 -bipyridine is formed. This compound is readily oxidized and hydrolyzed by moist air to 4,4 -bipyridine. Various oxidizing agents assist in the conversion to 4,4 -bipyridine. By-products from the reaction include 1,1 -diacetyl-l,T-dihydro-4,4 -bipyridine. This method of synthesizing 4,4 -bi-pyridine has frequently been used. ° The reduction of pyridine in acetic anhydride by catalytic hydrogenation instead of by zinc dust is less satisfactory because of the formation of other reduction products. Several variations and improvements in the Dimroth reaction have subsequently... 

This type of Dimroth rearrangement is strongly influenced by inductive and less by steric effects Dimroth reactions, usually reversible, almost always proceed, in the case of TPs, from the kinetically favored [4,3-a] product to the thermodynamically more stable [1,5-u] isomer (70CB3266 80PAC1611 87JHC805, 87M601). 

Dimroth-type rearrangements are well documented in fused pyrimidines such as in [l,2,4]triazolo[4,3-a]pyrimidines and [l,2,4]triazolo[4,3-c]pyrimidines under acid or alkaline conditions. The same type of reaction will occur in pyrimidines fused to azoles containing other heteroatoms. Thus, the pyrimidines (695) undergo the Dimroth reaction under both acid and alkaline conditions to furnish the rearranged compounds (696) (74JOC3783). 

A scH alled reverse Dimroth reaction is possible using the differing electron effects produced by methyl and methoxy groups on the ease of rearrangement. " In this way a 6-methylaminopurine, after prior conversion to the 1-methoxy derivative (51), rearranges readily to the 6-methoxyimino-... 

Bipyridyl can also be prepared from pyridine by the Dimroth reaction at a yield of about 60%. Pyridine is reduced in acetic anhydride with zinc dust to give amide, which is then oxidised and hydrolysed to 4,4 -bipyridyl of good purity. 

A simple thermal modification was communicated by L Abbe and Beenaerts at the Univeristy of Leuven. While preparing triazoles to study the thermal ramifications of electron-withdrawing N-l substituents on 1,2,3-triazoles, they discovered that lowering the temperature profile of the Dimroth reaction to 0-20 °C prevented the Dimroth rearrangement. Significant to this report was the first successful isolation of the triazole 18 from the reaction of 4-nitrophenzyl azide (16) with ethyl cyanoacetate (17). 

---