Rings thiophene

When benzene is prepared from coal tar it is contaminated thiophene from which it cannot be separated by distillation because of very similar boiling points Shaking a mixture of benzene and thiophene with sulfuric acid causes sulfonation of the thiophene ring but leaves benzene untouched The sulfonation product of thiophene dissolves m the sulfuric acid layer from which the benzene layer is separated the benzene layer is then washed with water and distilled Give the structure of the sulfonation product of thiophene... 

Excellent evidence of the gende nature of quinones as oxidants in the presence of the thiophene ring, eg (39), has been found (26). 

Preparative Methods. The thiophene ring system has been synthesized through numerous reaction types. A systematic review of these has been made (28) and is based on the number of components utilized in the constmction of the ring. Some 19 combinations are possible, utilizing five method types. Not all combinations have been reported and some would be of only minor benefit. 

TicarcHHn [34787-01-4] (SB) (52) is a significant penicillin antibiotic that incorporates the thiophene ring system. A number of routes to the required intermediate, 3-thiophenemalonic acid [21080-92-2] have been used over the years. Those from thiophene-based starting materials have involved 3-methylthiophene and 3-bromothiophene. 

Other Pharmaceuticals. Other pharmaceutical products incorporating the thiophene ring include the antiasthmatic dmg Ketotifen [34580-13-7] (Sandoz) (53), which is particularly marketed in Japan. The antifungal dmg Tioconazole [65899-73-2] (Pfizer) (54) is based on... 

Quantitative data are available on the effect on electrophilic substitution reactions of the fusion of a benzene ring to the b face of a furan or thiophene ring. The overall effect is to decrease reactivity this decrease is much more pronounced in the case of fusion to a furan than to a thiophene ring. As a consequence the overall reactivities of benzo[Z)]furan and benzo[Z)]thiophene are approximately equal 71AHC(13)235). 

The so-called ionic method for hydrogenating thiophenes (78T1703) is a further illustration of the chemical consequences of protonation. Protonation of the thiophene ring renders the ring susceptible to hydride ion attack, conveniently derived from triethylsilane (Scheme 12). 

It is estimated that thiophene reacts with phenyl radicals approximately three times as fast as benzene. Intramolecular radical attack on furan and thiophene rings occurs when oxime derivatives of type (112) are treated with persulfate (8UCS(Pt)984). It has been found that intramolecular homolytic alkylation occurs with equal facility at the 2- and 3-positions of the thiophene nucleus whereas intermolecular homolytic substitution occurs mainly at position 2. 

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

The 2-thienylthiourea (245) on oxidation with bromine in acetic acid gave the thieno[3,2-djthiazole (247). It has been suggested that the intermediate electrophilic sulfenyl bromide adds to the 2,3-bond of the thiophene ring to form (246) when then loses HBr to give (247) (71AJC1229, 78JHC81). Pyrazolo(3,4- /]thiazoles are formed in a similar fashion (76GEP2429195). 

Nitration of 4-(2-thienyl)- (301) and 4-(3-thienyl)-pyrazoles (302) mainly occurs on the thiophene ring, but when acetyl nitrate is used as the nitration agent small quantities of products nitrated on the pyrazole ring are isolated (position of the nitro group uncertain) (80CS( 15)102). Pyrazol-l -ylpyridines (303) undergo electrophilic reactions (bromination, chlorination and nitration) preferentially in the pyrazole ring. Thus, the nitration of (303 R = R = = H) either with a mixture of nitric acid and sulfuric acid at 10-15 °C or with... 

Fluorination of thiophene-2,5-dicarboxylic acitl with a sulfur tetrafluoritie-hydrogen fluoride mixture provides 2,5-bis(trifluoromethyl)thiophene in a 69% yield no fluorine addition to the thiophene ring occurs [229J. Also, imidazole mono- and dicarboxylic acids yield only the respective trifluo-romethyliinidazoles [230],... 

In 1910, Hinsberg described the reaction between benzil and diethylthiodiacetate, resulting in the preparation of the thiophene ring system. The reaction was run under Claisen condensation conditions, and after hydrolysis with aqueous acid at reflux, the free dicarboxylic acid 1 was produced. 

The foregoing resonance structures describe the influence of the substituents on the 7r-electron distribution in the thiophene ring. Besides this effect the inductive effect of the substituents on the a-electi on system must be considered when discussing physical and chemical properties of thiophenes. 

The ease of formation of the thiophene ring is also evident from the fruitless attempts to prepare 3,4-dimethylene tetrahydrothio-phene, which only lead to the formation of 3,4-dimethylthio-phene. 

C. Electrophilic Substitution of Compounds Containing Several Thiophene Rings... 

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