3- Amino-4- thiophene, reaction with aldehydes

Trialkylsilicon, germanium or tin derivatives have been introduced at position 5 of thiophene-2-carbaldehyde via lithiation <92S954>. The first step is the protection of the aldehyde as the amino-alkoxide by reaction with lithium A(-methylpiperazide (LNMP). Subsequent treatment with BuLi followed by R MCl and hydrolysis by cold brine gave the desired products. 

The reaction of 2,6-dioclyl-4,8-diethynyl-benzo[l,2-b 4,5-b ]dithiophene with dibromide compounds in toluene by Pd/Cu-catalyzed Sonogashira coupling copolymerization produced the polymers PEBBDT and PEBTTZ. Thiophene-3-carboxylic acid was similarity converted into the 2,6-Dioctyl-4,8-diethynyl-benzo [l,2-b 4,5-b ]dithiophene as the synthesis of common BDT compound [72]. EoUowing a three-component reaction, aldehyde, sulfur, and cyanoacetate of the 2-aIkyl substituted thiophene unit was converted into 2-amino thiophene [73]. The compound was obtained in good yield by the reaction of deamination and hydrolysis. PEBBDT was readily soluble in organic solvents like chloroform, THE, chlorobenzene (CB), etc. at room temperature but PEBTTZ was less soluble in these solvents [71]. 

Dieckmann-type reaction mechanism and not through a Stobbe-type reaction mechanism, as is the case in the Hinsberg reaction with oc-diketones. The usefulness of the Gewald reaction for the synthesis of 2-amino-3-carbonyl-substituted thiophens, important building-blocks for the synthesis of fused thiophens, has clearly been demonstrated. From the condensation products of cycloalkanones and nitriles (1), the thiophens (2) were obtained through the reaction with sulphur in the presence of diethylamine. Similarly, from the dithiacyclo-octane derivative (3), the thiophen (4) was prepared. In connection with the synthesis of psychophar-maca of the diazepine type, several substituted 2-amino-3-benzoylthiophens (5) were prepared through the reaction of phenacyl cyanides with aldehydes... 

Raney nickel desulfurization has been applied especially to the synthesis of different kinds of amino acids. a-Amino acids have been prepared by the Strecker synthesis of substituted thiophenealdehydes, followed by desulfurization of the thiophene a-amino acids. a-Amino-n-enantic acid, a-amino-n-caprylic acid, and norleucin have been obtained in about 50% yield from the appropriate thiophene aldehydes. From the desulfurization of thiophene -amino acids, obtained from the reaction of thiophenealdehydes with malonic acid in ammonia, aliphatic j8-amino acids, isolated as acetates, have been obtained in high yields. The desulfurization of 3-nitrothiophenes, such as (232), in ammonia leads to y-substituted amino acids (233). ... 

Two years later, Marko et al. reported an improved catalytic system which only required 0.25 equivalent of potassium carbonate instead of 2 equivalents (89). The oxidation reaction described above is dramatically influenced by the nature of the solvent. Thus, if the reaction was performed in fluorobenzene, total conversion of undecan-2-ol to undecan-2-one could be reached with 0.25 equivalent K2CO3, whereas 2 equivalents of base were necessary in toluene to convert 90% of this secondary aliphatic alcohol (Table VI). These optimized conditions were applied to a variety of functionalized alcohols and the results are reported in Table VII. The catalyst tolerates both sulphur and nitrogen substituents on the substrate. Indeed, (thiophen-2-yl)methanol, N-protected (S)-valinol or (S)-prolinol could be oxidized to the corresponding aldehydes with very good yields. In addition, no racemization was detected for the two P-amino alcohols as well as for (2S,5i )-2-isopropyl-5-methylcyclohexanol. The hindered endo- and exo-borneol are both converted to camphor with similar reaction rates, despite their distinctly different steric properties. 

A library of novel 5-amino-2,7-diaryl-2,3-dihydrobenzo[l)]thiophene-4,6-dicarbonitriles was synthesized by a one-pot domino reaction of 5-aryldihydro-3(2H)-thiophenes, malonitrile, and aromatic aldehydes in the presence of morpholine (13BMCL2101). A mechanism was proposed that involves a sequence of Knovenagel condensation, Michael addition, intramolecular Thorpe-Ziegler cyclization, tautomerization, and elimination. The compounds were evaluated for their AChE (acetylcholinase) activity. The 5-amino-2,7-bis(4-methoxyphenyl)-2,3-dihydrobenzo[l)] thiophene-4,6-dicarbonitrile was found to be the most potent with IC50 4.16 xmol/L. 

Thiophen Analogues of Quinoline.— Interest in the chemistry of thieno-pyridines is continuing. Thieno[3,2-b]pyridine has been prepared in 80% yield through the zinc-chloride-catalysed condensation of 3-aminothiophen hydrochloride with malonic aldehyde acetal. Reaction of the 2-amino-3-benzylthiophen (425) with l-nitro-2,2-bis(methylmercapto)ethylene (426) gave the thieno[2,3-b]pyndine derivative (427) in 29% yield. 5-Ethylthieno-... 

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