Modification of the Orientation of Substitution Reactions on Thiophene and Furan Derivatives

Abstract

Under normal conditions, thiophene and furan derivatives are substituted in the α position, and no convenient alternative methods for the preparation of β‐substitution products have been available until now. The present article describes a method that permits the synthesis of many β‐substituted thiophenes and furans. In this method, the carbonyl group in α‐aldehydes or ketones of the thiophene and furan series is blocked by complex formation with an excess of aluminum chloride, so that electrophilic substitution takes place in position 4. In another useful method, the carbonyl group is blocked by acetalization. The acetals can be metalated in the ring by organolithium compounds.

Mono-, di-, and trisubstituted acyl and alkyl thiophenes. I. Synthesis, ultraviolet, and proton magnetic resonance spectra

“…The aromatic protons for the various compounds (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) provided the classic resonances for substituted thiophenes.…”

The synthesis and mesogenic behaviour of the first series of low molar mass thieno[3,2-b]thiophene-2-carboxylate ester-based mesogens

“…Resonance arguments suggested that electrophilic aromatic substitution on these carboxylate ester derivatives would take place at the unsubstituted a-position with high levels of regioselectivity. Using related thienyl and thieno[3,2-b]thiophene substrates [29][30][31][32] as model systems we chose to brominate 3 using N-bromosuccinimide in a mixed solvent system (chloroform/acetic acid, 1:1). Under these conditions the bromination of 3 was achieved with complete a-regioselectivity in 87% yield.…”

Reactions of halothiophenes with metal amides. Convenient preparation of .beta.-bromothiophenes

“…2 Unfortunately, only the a-bromothiophenes are readily available by direct electrophilic substitution.2 Consequently, several indirect methods for introducing substituents into the ß position of thiophenes have been developed. 3 Nevertheless, ß-bromothiophenes, because they can be converted quantitatively to the versatile ß-lithio derivatives,4 are still viewed as the most suitable entry into the ß-substituted thiophene series. 3,5 The synthesis of 3-bromoand 3,4-dibromothiophene usually involves exhaustive bromination of thiophene to 2,3,5-tribromo-and 2,3,4,5-tetrabromothiophene, respectively, followed by selective removal of the 2 and 5 bromine atoms with Grignard reagents,6 lithium reagents,7 or zinc and acid.8,9 Substituted ß-bromothiophenes often require even more elaborate synthetic procedures.…”

“…3 Nevertheless, ß-bromothiophenes, because they can be converted quantitatively to the versatile ß-lithio derivatives,4 are still viewed as the most suitable entry into the ß-substituted thiophene series. 3,5 The synthesis of 3-bromoand 3,4-dibromothiophene usually involves exhaustive bromination of thiophene to 2,3,5-tribromo-and 2,3,4,5-tetrabromothiophene, respectively, followed by selective removal of the 2 and 5 bromine atoms with Grignard reagents,6 lithium reagents,7 or zinc and acid.8,9 Substituted ß-bromothiophenes often require even more elaborate synthetic procedures. 10,11 This paper reports an alternative synthesis of a variety of ß-bromothiophenes (2) which does not require the preparation of intermediate polybromothiophenes but proceeds directly by rearrangement of the easily prepared2 or commercially available -bromo isomers (1).…”

“…Chem., 515, 273 (1935). Product thiophene 3-Iodo (77%) 76% recovery 2f (38%); 2,3,4-tribromo (36%) 2f (46%); 2,3,4-tribromo (38%) 2f (34%); 2,3,4-tribromo (49%) 2e (21%); 2-methyl-3-bromo (21%); 2,3,4-tribromo-5-methyl (9%) 2f (80%) " Unless otherwise noted, all reactions run as follows: 0.1 mol of reactant, 0.2 mol of anilide, 20 min, NH3(1), -33°, no other thiophene products in >1% yield. b 0.6 mol of anilide, 15 min, 5% side product.…”