Thieno-pyridines electrophilic substitution

Electrophilic substitution in benzo[fe]thieno- and benzo[fe]furo-[2,3-c]pyridines (2) occurs mainly at the 6-position, although when this position is blocked by Cl in a related structure 5-,7-, and 8-substituted products are formed. The usefulness of triflu-oromethanesulfonic acid as a new solvent with CFCI3 for the reaction of fluorine with aromatics has been explored. Fluorobenzene gives 1,4-difluorobenzene (31%) and 1,2-difluorobenzene (7%) instead of the addition products mainly observed when the acid is absent 1,2- and 1,3- but not 1,4-difluorobenzene undergo further substitution at appropriate acidity. 

Deuteration in deuteriosulfuric acid of some derivatives of thieno fused diazaborines was studied by NMR spectroscopy. It was found that the pyridinic nitrogen was protonated and that deuteration occurred in the thiophene ring of the protonated molecule. In conformity with the above-mentioned electrophilic substitutions, the thiophenic /3-positions were more reactive than the a-positions. Isosteric thienopyridines showed similar reactivity and it was thus concluded that the systems were related (77JHC893). 

Electrophilic substitution reactions of thieno[3,2-cf pyridine occur at position 7 (equation 38). With dimethyl sulfate in an alkaline medium, thieno[3,2-cf pyrimidin-4-one (347) yields an N-methyl derivative. 

The results of the work on electrophilic substitution of thieno-pyridines confirm the general predictions of electron distribution calculations, i.e.. that substitution should occur preferentially / to the sulfur atom. Although relative rate data are lacking, qualitatively it would seem that the systems are even more resistant to attack than the isosteric quinoline and isoquinoline. 

Klemm and his colleagues have used simple molecular orbital (MO) theory to obtain electron densities (q, for position r) and have calculated superdelocalizability values for electrophilic St) and nucleophilic (St) substitution for thieno 2,3-f>l-, J- 3,2-b -75 - 3,4-61-40, and -13,4-c]-40 pyridines. Similar calculations for the [2,3-cl-isomer have been conducted by Dressier and Joullie.48 The results are collected in Table I. 

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