Thiophenes annelations

A thiophene-annelated thiadiazole has been prepared from hydrazone 47, which was obtained from the thiolactone 46. Reaction of the hydrazone at room temperature with thionyl chloride resulted in an 8 1 mixture of 48 and 49. Heating the reaction to 80°C in dichloroethane provided 48 exclusively. ... 

There is considerable interest in the chemistry of triazines as some of these compounds show pronounced antimalarial, antimicrobial and antiviral activity (76JCS(Pl)252l). Therefore two types of thiophenes annelated with a triazine ring will be mentioned. Thieno[2,3-d]-1,2,3-triazines were synthesized by cyclization of diazotized 2-aminothiophene-3-carboxamides (equation 55) (73M1586). Treatment of 3-alkylthio-6-styryl-5-oxo-2,5-dihydro-l,2,4-triazines with phosphorus pentasulfide in pyridine yields thieno[2,3-e]-l,2,4-triazines (equation 56) (78CI(L)585). Probably a thiation with subsequent cycloaddition and elimination of a hydride ion is involved. 

The same general methodology, the reaction of the ditellurolate dianion 68 with tetrachloroethylene, was employed for the synthesis of the thiophene-annelated TTeF. Compound 69 was obtained in 75% yield (83MI1 84JA8303 85MI2). No formation of the possible six-membered ring derivative was reported. 

Cycloaddition of ethylthiocolchicine 650 with 2 molar equiv of cyclooctyne affords thiophene-annelated homo-barrelenones 651 and 652. The authors propose a reaction sequence including a consecutive [4- -2]/[3- -2] cycloaddition (Equation 36) <1998EJ02451>. 

The group of Pal [51] reported an interesting sequence to thiophene-annelated a-pyrones 29 and 30 in good yields based upon the Sonogashira catalyst system (Scheme 12.19). Although the mechanistic rationale for this pseudo-three-component synthesis remains obscure because an oxidation step has to be formally Involved, the cooperatlvlty of the palladium-copper system is remarkable. 

One of the more useful predicative applications of the relatively crude Hiickel method has been to illustrate quantitatively the effect of benzenoid annelation on the resonance energies of furan and thiophene. The results are summarized in Figure 1. As expected, thiophenes are more stable than the corresponding furans and 3,4-fusion results in less stable compounds than 2,3-fusion (77CR(C)(285)42l). 

This chapter follows the organization used in the past. A summary of the electronic properties leads into reports of electrocyclic chemistry. Recent reports of studies of HDS processes and catalysts are then summarized. Thiophene ring substitution reactions, ring-forming reactions, the formation of ring-annelated derivatives, and the use of thiophene molecules as intermediates are then reported. Applications of thiophene and its derivatives in polymers and in other small molecules of interest are highlighted. Finally, the few examples of selenophenes and tellurophenes reported in the past year are noted. 

The efficient synthesis of dithicno[2,3-A 32 -r/ thiophenes 12 has been achieved from 3-bromothiophene 298 <2006JOC3264>. The sequence of a-connection and [l-annelation afford annulated [1-trithiophene 12 (Scheme 54). Optimization of reaction conditions (solvent and temperature) for the a-connection step provides significantly improved yields compared to earlier report. 

A general synthesis of dibenzo-annelated dithieno[3,Z-b Z, 3 - thiophene 18 has been reported from bis(o-hydro-xyl)diacetylenes. This cyclization constructs a fused tricyclic skeleton in one pot. The subsequent dechalconization with copper powder produces a series of thiophene and selenophene-based heterocenes (Scheme 64) <20050L5301>. 

Potts and co-workers have used phosphorus pentasulfide and pyridine as a standard reagent for constructing annelated diphenylthiophene rings from o-dibenzoyl compounds. Many of these annelated thiophenes can be written only in the tetracovalent sulfur or ylid dipolar form (96) and are thus termed nonclassical 123 other examples, particularly of the synthesis of non-classical thienoisothiazoles, have been reported by Gotthardt.124... 

The electron-rich thiophene ring system can be elaborated into complex, fused thiophenes by acid-mediated intramolecular annelation reactions. For example, treatment of alcohol 96 with trimethylsilyl triflate promoted a Friedel-Crafts acylation and subsequent dehydration giving benzo[b]thiophene 97, a potential analgesic <00JMC765>. Treatment of ketone 98 with p-toluenesulfonic acid resulted in the formation of fused benzo[b]thiophene 99 <00T8153>. Another variant involved the cyclization of epoxide 100 to fused benzo[f>]thiophene 101 mediated by boron trifluoride-etherate . 

Dewar185-187 reported the first six-membered aromatic rings containing boron, oxygen, and nitrogen heteroatoms, and later Gronowitz188 prepared similar systems annelated with thiophene. The chemical reactivity and NMR data indicate electronic delocalization. 

The bromination of annotated thiophene derivatives appears to quite substrate-specific. While bromination of 3,4-dimethylthiophene (54) leads to substitution, the bromination of cyclobutathicqthene derivatives (54-56, Figure 7) leads exclusively to addition products. It has been speculated that annelation induces localiza-... 

The lability of thieno[3,4-6]thiophene (3) and other iso-annelated systems, such as benzo[c]thiophene and benzole] furan, may be due to the strain effect (Mills-Nixon effect see also Zwanenburg et alP and references therein) in the condensed five-membered ring. The stability of the iso-annelated dithienothiophenes 7—9 is noteworthy. Simple LCAO MO method calculations on benzo[c]thiophene indicate that its instability is due to low specific delocalization energy and high free valence index at position 1. 

The electron-rich thiophene ring system can be annelated by intramolecular Friedel-Crafts acylation reactions to give fused thiophenes <99IJC648, 99JMC2774>. The synthesis of a thiophene isostere of ninhydrin involved an intramolecular Friedel-Crafts acylation <99SL1450>. Specifically, treatment of thiophene 86 with thionyl chloride followed by aluminum chloride gave annelated thiophene 87. The synthesis of isothianinhydrin 88 was then accomplished in six steps from 87. 

Annelation of a furan ring onto a thiophene is also possible by flash vacuum pyrolysis at 650 °C of the acrylate 368 and malonate 369, which gave 2-(methylthio)thieno[3,2-/ ]furan 370 and methyl-5-(methylthio)thieno[3,2- ]furan-2-carboxylate 371, respectively, in yields of 21% and 22% <1997J(P1)2483>. 

This approach is used exclusively for the synthesis of the isomeric annelated isothiazoles and isoselenazoles to form the nitrogen-sulfur(selenium) bond and has been discussed in CHEC-II(1996) <1996CHEC-II(7)49>. A wide variety of oxidative cyclizations have been reported, some of which incorpotate an amination. Eor example, reaction of 47 with chloramine gives the corresponding isothiazolo[5,4-7]thiophene 40 (Equation 9) <2000P65>. 

These methods are limited in scope. Direct thiation has been reported for the transformation of vicinal diketones to [3,4]-annelated thiophenes <1996CHEC-II(7)49>. Thionations and selenations of vicinal halomethyl ketones with thioacetamide or iV,iV-diethylselenopropionamide as sulfur and selenium donors, respectively, have also been reported <1996CHEC-II(7)49>. In a recent example, thieno[3,4-f]pyrazoles 160 were readily prepared from aryl 5-bromomethyl-l//-l-phenylpyrazole-4-yl ketones 159 by reaction with thioacetamide (Equation 35) <1998JHC71>. Additionally, an example of an amination cyclization by reaction of 161 with benzylamine to afford pyrrolo[3,4-i/ thiazole 162 has been described (Equation 36) <1998JHC71>. 

Preparation the linear tropone-annelated benzo [c] furans 371 (X = O) by direct condensation of dialdehyde 370 (X = O) with acetone, 1-phenyl-acetone, and 1,3-diphenylacetone, in alkaline medium was—in contrast to the corresponding benzo [c]thiophene (X = S)—unsuccessful. Interestingly, this condensation has been brought about with the Diels-Alder adduct 372 subsequent heat yields 371 (X = O), a rare case where V-phenylmaleimide is used as a protective group. Compounds 371 react with V-phenylmaleimide even at room temperature to give adducts 373. 

Other five-membered heterocycles such as thiophenes, thiazoles and oxazoles have been successfully annellated in the anthraquinone series. For example, the yellow dye (12) may be prepared from 2,6-diaminoanthraquinone by condensation with benzotrichloride and sulfur. Similarly, the six-membered heterocycles acridines, quinoneazines, pyrazines, acridones and pyrimidines are frequently incorporated (B-52MI11201). In fact, the best known of the anthraquinone vat dyes are indanthrone (13) and flavanthrone (14). The former anthraquinoneazine, a beautiful blue, which was the first such structure to be manufactured on a large scale, may be prepared by alkali fusion of 2-aminoanthraquinone at 220 °C (27MI11200). Treatment of 2-aminoanthraquinone in nitrobenzene with antimony pentachloride yields the yellow flavanthrone (14), the structure being confirmed by Scholl (07CB1691). Both indanthrone and flavanthrone and their derivatives have attracted considerable commercial attention. 

In more esoteric compounds like (50) (78JA4326) and (51) (78CB1330) there is no reported tendency for cycloadditions to occur. A doubly protonated cation of undetermined structure reportedly forms on protonation of (50), however. Benzo[6 ]thiophenes can be annelated in a similar manner as occurs with (52) (79JOC2491). The question of the localization of double bonds in benzo[c] fused heterocycles continues to attract theoretical interest (77JA8248). 

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