Synthesis of thieno-[2,3-b]-, -[3,2-b]- and -[3,4-b]-thiophenes and thieno-[3′,2′:4,5]-, -[2′,3′:4,5]- and -[3′,4′:4,5]-thieno[3,2-d]pyrimidin-7(6H)-ones starting from thiophene

3-Bromo-, 3,5-dibromo- and 3,4,5-tribromo-2-thienyllithium have been prepared by bromine → lithium exchange and converted into a number of thiophene derivatives, including the corresponding 2-carbaldehydes. The aldehydes have been converted into the corresponding thiophene 2-carbonitriles. Metallation of 2,5-dibromo- or 2,4,5-tribromo-thiophene with LDA occurred at a vacant 3-position but the resulting 3-lithiated thiophenes rearranged (mechanism discussed) to 3,5-dibromo- and 3,4,5-tribromo-2-thienyllithium, which were quenched with various electrophiles. Attempts to dilithiate 2,5-dibromothiophene with LDA were unsuccessful. 3,4-Dibromo-2,5-dilithiothiophene was prepared from 2,3,4,5-tetrabromothiophene but it failed to yield the 2,5-dicarbaldehyde with N,N-dimethylformamide. The title thienothiophenes were prepared by reaction of a 3-bromothiophene-2-carbaldehyde, a 2-bromothiophene-3-carbaldehyde (prepared by bromination of a thiophene-3-carbaldehyde) or a 4-bromothiophene-3-carbaldehyde, or a corresponding nitrile, with ethyl 2-sulfanylacetate or 2-sulfanylacetamide. Thienothiophenes carrying an o-aminocarboxamide substitution pattern gave the title thienothieno[3,2-d]pyrimidinones with triethyl orthoformate.