Functional derivatives of thiophene. I. Synthesis and ¹H‐NMR spectra in the 2‐aminothiophene series

Abstract

T h e preparation of 2-amino-5-nitrothiophene, Z-formamido-5-nitrothiophene, 2-acetamido-5nitrothiophene and 2-t-butyloxycarbonylarnino-5-nitrothiophene are described. Abnormal values of the coupling constants J3,4 had been observed in the 'H-nmr spectra of compounds obtained. J. Heterocyclic Chem., 18, 851 (1981).Aminothiophenes have become important intermediates for the synthesis of condensed thiophene derivatives. In connection with a general program directed to the study of such systems, we have prepared 2-amino-5-nitrothiophene (1). It is known that 2-aminothiophenes tend to be unstable in the absence of electron-withdrawing groups in the 3or 5-position. However, 2-amino-5-nitrothiophene (1) has not been previously described in the literature. In the present work we wish to report the preparation and the nmr spectra of 1 and related compounds.Of the different synthetic methods for the preparation of 2-aminothiophenes (l), the rearrangement of acyl azides to formamido derivatives is a widely used method. Thus, we attempted the synthesis of compound 1 from the acyl azide 2 as a precursor (cf. Scheme 1).Compound 2 was prepared from the acid chloride 3 (2). By the action of sodium azide on compound 3, a yellow solid was obtained in almost quantitative yield. This product was identified as the acyl azide 2 (3).Scheme I 4 2 T The formamido derivative 4 was prepared according to the method of Stevenson and Johnson (4) by the reaction of compound 2 with formic acid. The formyl proton was readily identifiable in the nmr spectrum appearing as a doublet at 8.8 ppm. This splitting is due to the restricted rotation of the formyl group. The coupling constant showed a value of 1.5 Hz (5). Several methods for cleaving the formyl group in 4 were tested (6). Under mild conditions 85 1 (dilute acid or alkali, room temperature) the formamido compound 4 was recovered unchanged. Under drastic conditions desulfurization resulted giving tarry products.In view of these results we tested the preparation of compound 1 from its t-butyloxycarbonyl derivative 5, according to Binder, et al., (7). By reaction of compound 2 with t-butyl alcohol in dry dioxane, compound 5 was obtained in 70% yield. When 5 was treated with anhydrous hydrogen bromide in an aprotic solvent (methylene chloride) a crystalline product was obtained. The melting point of this solid changed with time. This fact can be explained by the loss of hydrogen bromide from the salt (1 .HBr), due to the weak basicity of the amino compound 1. Drying this crystalline substance in a desiccator under vacuum with potassium hydroxide allowed us to isolate the free base 1. This product proved to be stable for 48 hours; after this time compound 1 darkens and polymerizes to a tar in contact with air. When it is stored under a vacuum or under a nitrogen atmosphere, the amine is stable for several days.By reaction of compound 1 with acetic anhydride, the N-acetyl derivative 6 was obtained in 60% yield (8). Spectral data and analyses were consistent with the structures of compounds 1 , 2...

Efficient Syntheses of Some New Thiophene‐Based Heterocycles

“…Thus, treatment of (2) with ophenylenediamine in ethanol catalyzed by triethylamine under reflux afforded a reddish brown product identified as 2,4-diamino-benzo[b] [1,4]diazepine derivative (8). The IR spectrum of the latter product was free of nitrile functions and revealed new absorption bands at 3308-3229 cm H-NMR spectrum of (8) supported its structure, as it revealed new broad singlet signal at δ 8.14 ppm assignable to two NH 2 protons.…”

A Facile Synthesis of 3-Substituted-2-aminothiophenes and 1,3-Disubstituted-2-methylthiopyrroles

“…Since the first reported preparation of 2-aminothiophene, the synthesis of functionalized aminothiophenes has been studied extensively . Four main synthetic approaches have been applied, three of which utilize preexisting thiophene rings: (i) reduction of nitro- or nitroso-thiophenes, (ii) Beckmann, Schmidt, or Curtius rearrangements of thiophenecarboxylic acid derivatives, and (iii) nucleophilic displacements in mercapto- or iodo-thiophenes with amines. Route (iv), ring closure reactions from non thiophene starting materials, is less developed for the preparation of simple 2-aminothiophenes.…”