Synthesis thiophene systems

Substituted 3-hydroxythiophenes are convenient starting-points for the synthesis of the thieno[3,2-6]thiophene system. Shvedov et a/.89 obtained 50% of 3-chloro-3-ethoxycarbonyl-5-methylthiophene-2-aldehyde (110) from 3-ethoxycarbonyl-4-hydroxy-2-methylthiophene (109) by Vilsmeier formylation at 100°. Reaction with thioglycolic ester formed 3-ethoxycarbonyl-5-methoxycarbonyl-2-methylthieno[3,2-61-... 

Synthesis, of tetracyclic and penlacyclic condensed thiophene systems. 32, 127 Synthesis and reactions of l-azirines. 13, 45 Synthesis of heleroeycles through nucleophilic additions to acetylenic esters, 19, 279... 

Condensed thiophene systems, tetra- and pentacyclic, 32, 127 Condensed 1,2,4-triazines I. Fused to heterocycles with three-, four-, and five-membered rings, 59, 39 Condensed l,2,4-triazolo[3,4-z] heterocycles, synthesis, 49, 277... 

Of the analogous parent heterocycles, benzo[c]pyrrole (isoindole),2 benzo[c]furan, and benzo[c]thiophene, only the last has proved sufficiently stable for isolation (see Sections II and IV). Although the first reference to the benzo[c]thiophene system in the literature was Leser s3 synthesis of l,3-dihydrobenzo[c]thiophene in 1884 (Section... 

Wrobel, J. T., and E. Hejchman, Spiro Derivatives of Tetrahydroth-iophene. Synthesis of the Quinolizidine (3-Spiro-2 )Tetrahydro-thiophene System Using Solid/Liquid or Liquid/Liquid Phase-Transfer Catalysis, Synthesis, 452(1987). 

Several routes involving thiophene ring synthesis towards more complex heterocycle fused thiophene systems should also be mentioned. Thus for example, the alkaloid thienodolin 56 has been prepared by reaction of l-(/ert-butoxycarbonyl)-2,6-dichloroindole-3-carboxaldehyde with 2-mercaptoacetamide <04EJO2589>, while a double cyclization of 2,6-dichloropyridine-3,5-dicarbonitrile or the corresponding pyrazine derivative with ethyl 2-... 

The synthesis of the anti-inflammatory agent Prifelone is an example of the application of the basic chemistry of the thiophene system in the constmction of valuable pharmaceutical agents. Here, a substituted benzoyl chloride reacts in the Friedel-Crafts manner with thiophene flie attack occurs at the alpha position (Scheme 9.14). 

The Vilsmeier-Haack reaction has been used in die synthesis of thiophenes with potential anti-inflammatory properties. The electron-rich ring of the thiophene system makes it an ideal nucleophile for the Vilsmeier-Haack... 

Preparation of 2-benzo[6]thienyl-lithium followed by its reaction with butyl borate and oxidation of the intermediate boronic acid derivative has been used for the synthesis of the 2-hydroxybenzo[6]thiophen system (thio-... 

Pemsal of Table 14.5 leads to the clear conclusion that considerably less data are available on the synthesis of aryl-heteroaryl (Ar-HetAr) derivatives based on the DoM-cross-coupHng nexus [43-47]. Thus in the ArB(OH)2 -5-ring HetArLG cross-couphng series (entries 1-9), indoles, furans, and thiophene systems have been... 

Synthesis of Fused Heterocycles. Use of chloroacetyl chloride in the reaction with l-[(trimethylsilyl)methyl]benzotriazole opens new possibilities. Thus, the l-(benzotriazol-l-yl)-3-chloroacetone obtained in the first step is further reacted with 2-mercaptobenzothiophene to give l-(benzotriazol-l-yl)-3-[(benzothiophen-2-yl)thio]acetone in a practically quantitative yield (eq 8). Cyclization of the obtained acetone derivative with ZnCl2 readily provides 3-[(benzotriazol-l-yl)methyl][2,3-ft]benzothiophene (eq 9). The structure can be further modified by subshtufion of the benzotriazolyl moiety with other groups. Preparation of several other fused thiophene systems, starting from other aryl mercaptans, is also reported. ... 

A convenient method for the synthesis of the borepino[3,2-b 6,7-b]di-thiophen system (498) has been worked out. By comparing its spectral properties with those of the corresponding dihydro-derivative and with the isoelectronic dithienotropylium ions, some evidence for aromatic stabilization was obtained. The chemistry of another boron-containing fused thiophen system (499) has been studied. ... 

Thiophene [110-02-1] and a number of its derivatives are significant in fine chemical industries as intermediates to many products for pharmaceutical, agrochemical, dyestuffs, and electronic appHcations. This article concentrates on the industrial, commercial, and economic aspects of the production and apphcations of thiophene and thiophene derivatives and details the main synthetic schemes to the parent ring system and simple alkyl and aryl derivatives. Functionalization of the ring and the synthesis of some functional derivatives that result, not from the parent ring system, but by direct ring cyclization reactions are also considered. Many good reviews on the chemistry of thiophene and thiophene derivatives are available (1 7). 

Interesting results have been obtained in intramolecular acylation reactions involving pyrrole and thiophene derivatives. A muscone synthesis involves selective intramolecular acylation at a vacant a-position (Scheme 18) (80JOC1906). In attempts to prepare 5,5-fused systems via intramolecular acylation reactions on to a jS-position of a thiophene or a pyrrole, in some cases ipso substitution occurs with the result that rearranged products are formed (Scheme 19) (82TH30200). 

Another significant advance of the Hinsberg thiophene synthesis has explored the reactivity of diketosulfides in place of the use of diethylthiodiglycolate. This process has been extensively utilized for the preparation of novel thiophene containing systems. With glyoxal as condensation partner, the utility of this method has been pioneered Miyahara et al. in the synthesis of novel thiophenophanes 19, 20, and 21. 

Another reagent system that has been recently employed in the Paal synthesis of thiophenes is the combination of bis(trialkyltin)- or bis(triaryltin) sulfides with boron trichloride. Known as the Steliou reagent,it has been utilized in the transformation of 1,4-diketone 11 to thiophene 12. Higher yields are obtained in shorter reaction times in contrast to the use of Lawesson s reagent. Additionally, others have noted the relative ease of the work-up procedure using the Steliou conditions, and the fact that the tributyltinchloride byproduct of the reaction is reusable. Similarly, the combination of the bis(trimethylsilyl)sulfide has been used in conjunction with trimethylsilyltriflate for the preparation of thiophenes in an analogous manner. ... 

The enormous literature of five-membered ring systems containing sulfur primarily describes the synthesis, properties and chemistry of thiophene and its derivatives279. 

A New Improved Synthesis of Tricycle Thienobenzazepines Apphcation of chemistry recently developed by Knochel" combined with the well-described halogen dance (HD) reaction, allowed preparation of our key intermediate A in only three synthetic transformations (Scheme 6.4). In this respect, treatment of 2-bromo-5-methylthiophene with hthium diisopropylamide followed by dimethylformamide afforded aldehyde 11 in good yield, lodo-magnesium exchange with conunercial 4-iodo-3-nitro anisole followed by reaction with 11 afforded the thiophene catbinol 12. Dehydroxylation of 12 provided our key intermediate A which presented the requisite functionality to examine our approach to the construction of the seven-member ring system. 

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