Ether-substituted thiophenes

There have been a number of different synthetic approaches to substituted PTV derivatives proposed in the last decade. Almost all focus on the aromatic ring as the site for substitution. Some effort has been made to apply the traditional base-catalyzed dehydrohalogenation route to PTV and its substituted analogs. The methodology, however, is not as successful for PTV as it is for PPV and its derivatives because of the great tendency for the poly(u-chloro thiophene) precursor spontaneously to eliminate at room temperature. Swager and co-workers attempted this route to synthesize a PTV derivative substituted with a crown ether with potential applications as a sensory material (Scheme 1-26) [123]. The synthesis employs a Fager condensation [124] in its initial step to yield diol 78. Treatment with a ditosylate yields a crown ether-functionalized thiophene diester 79. This may be elaborated to dichloride 81, but pure material could not be isolated and the dichloride monomer had to be polymerized in situ. The polymer isolated... 

Allyl- and benzyl-thiophenes may be cyclized by a direct Bradsher reaction, using dichloromethyl methyl ether or related dichloroalkyl methyl ethers and tin(IV) chloride catalysis to give the corresponding benzo- or dibenzo-thiophenes in 55-60% yield (73JCS(P1)1099). Thus substituted thiophenes having a benzyl group at either the 2- or 3-position, e.g. (349), when treated with a 1,1-dichloroalkyl methyl ether and tin(IV)... 

Roncali, J., R. Garreau, and M. Lemaire. 1990. Electrosynthesis of conducting poly-pseudo-crown ethers from substituted thiophenes. J Electroanal Chem 278 373-378. 

Because of possible ion-selective effects, pseudo-crown ethers were prepared by electropolymerization from suitably substituted thiophenes by Roncali et al. [1093]. The polymer formed from l,14-(3-thienyl)-3,6,9,12-tetraoxatetradecane showed an absorption maximum at A = 430 nm in the undoped state. Compared to the respective value for poly(3-(3,6,9-trioxade( l))thiophene, a blue shift of about SO nm, indicating a shorter mean conjugation length, was found. In the oxidized form, this band was considerably reduced in intensity, and a new band at A = 750 nm, attributed to a transition into the upper bipolaron band, was seen. The results were found to be inferior to those of polymers prepared from 3-polyether-substituted monomers. A general review of this field was provided by Fabre and Simonet [1094] for further details, see also [1095]. 

Endo adducts are usually favored by iateractions between the double bonds of the diene and the carbonyl groups of the dienophile. As was mentioned ia the section on alkylation, the reaction of pyrrole compounds and maleic anhydride results ia a substitution at the 2-position of the pyrrole ring (34,44). Thiophene [110-02-1] forms a cycloaddition adduct with maleic anhydride but only under severe pressures and around 100°C (45). Addition of electron-withdrawiag substituents about the double bond of maleic anhydride increases rates of cycloaddition. Both a-(carbomethoxy)maleic anhydride [69327-00-0] and a-(phenylsulfonyl) maleic anhydride [120789-76-6] react with 1,3-dienes, styrenes, and vinyl ethers much faster than tetracyanoethylene [670-54-2] (46). 

Nucleophilic substitution has been used for the preparation of many thiophenes. For instance, 2-phenylthio-3,4-dinitro-5-piperidino-thiophene (155) has been prepared " through stepwise reaction of (150) with different nucleophiles. Nitrothienols and derivatives of them have been obtained from halogenated nitrothiophenes. " Allyl ethers have been prepared by the reaction of 5-chJoro-4-nitro-2-acetylthiophene, 3-nitro-2-chlorothiophene, and 2-nitro-3-bromothio-... 

In attempting to extend the method to other activated aromatics, it was found that pyrroles give mixtures of 2- and 3-substituted products, and that naphthol ethers and benzo[6]thiophene fail to react. 

This gives tautomeric mixtures119 when the tert-butyl group is removed. The methyl ether has been used to obtain 3-hydroxy-2-carbonyl derivatives in the selenophene series.120 The unsubstituted 2-hydroxyselenophene system has been prepared by hydrogen peroxide oxidation of 2-selenophene-boronic acid.121 However, in the 5-methyl-substituted system deboronation became such an important side reaction that 5-methyl-2-hydroxyselenophene had to be prepared by acid-catalyzed dealkylation of 5-methyl-2-fert-butoxy-selenophene. Both 2-hydroxy- and 5-methyl-2-hydroxyselenophene exist mainly as 3-selenolene-2-ones (93) and for the 5-methyl derivative it was possible to isolate the / ,y-unsaturated form (92) and follow the tautomeric isomerization. The activation parameters thus obtained were compared with those for the corresponding furan and thiophene systems. 

Additional acylation studies were also reported (24), (26). In the first case it is claimed that acylation of thiophene is achieved by means of HC104 and acetic anhydride affording a 65 % yield of 2-acetylthiophene. In the second paper Levine and coworkers reported that while 2,5-dimethylthiophene could be readily acetylated, 2,5-dichlorothiophene acetylated sluggishly. This is, however, readily explained, since the presence of chlorine atoms on the thiophene ring decreased its reactivity in electrophilic substitution reactions. In the case of methyl substitution, however, the 3 and 4 positions of the ring are activated toward electrophilic substitution by the inductive and hyperconjugative effects. Thus 2,5-dimethylthiophene was successfully acylated by the boron fluoride etherate method in high yield with three aliphatic anhydrides. 

Dibenzothiophene has recently been synthesized from 2-allylbenzo-[fcjthiophene (24) by treatment with dichloromethyl butyl ether and anhydrous stannic chloride at low temperatures, as shown in Eq. (1) (55%). This sequence has been extended by the use of substituted allyl groups and modified formylating agents to yield dibenzothiophenes substituted in the 1-, 1,3-, and 3-positions. For example, treatment of 2-allylbenzo[6]thiophene with the modified formylating agent EtOCCl2-... 

Vinyl ethers and amines disclose little tendency to revert to type thus, the intermediate formed by reaction with an electrophilic reagent reacts further by adding a nucleophilic species to yield an addition compound cf the sequence (8) — (11). Thiophene and pyrrole have a high degree of aromatic character consequently the initial product formed by reaction of thiophene or pyrrole with an electrophilic species subsequently loses a proton to give a substituted compound cf the reaction sequence (12) — (15). Furan has less aromatic character and often reacts by overall addition as well as by substitution. In electrophilic addition, the first step is the same as for substitution, i.e. the formation of a tr-complex (e.g. 13), but instead of losing a proton this now adds a nucleophile. 

Alkyl- or aryl-dibenzothiophenes are conveniently prepared from the 2-arylthio-cyclohexanones, which are readily cyclized and dehydrogenated to yield the respective 1-, 2-, 3- or 4-substituted dibenzothiophenes (382 equation 9 Section 3.15.2.3.2). More complex polycyclic systems are available, using suitable aryenethiols, such as naph-thalenethiols, and 2-bromo-l-tetralone to synthesize the appropriate 2-arylthio ketones. Diaryl sulfides can be converted to dibenzothiophene derivatives in satisfactory yields by photolysis in the presence of iodine (equation 10) (75S532). Several alkyldibenzothiophenes with substituents in the 2- and/or 3-positions were prepared in satisfactory yield by the condensation of dichloromethyl methyl ether with substituted allylbenzo[6]thiophenes (equation 11) (74JCS(P1)1744). 

Acetylbenzo[6]tellurophene is also formed in isolable quantities. Benzo[6]selenophene is converted into 2-acyl derivatives by reaction with acid chlorides in the presence of aluminum chloride, whereas similar Friedel-Crafts acylation of benzo[6]thiophene yields 3-substituted products. When the 2-position is blocked, formylation can be directed into the 3-position. Thus treatment of 2-bromobenzo[6]selenophene with dichloromethyl butyl ether (Cl2CHOBu) and titanium tetrachloride yields the 3-formyl derivative (72BSF3955). If the 2- and 3-positions of benzo[6]selenophene are blocked with methyl groups, acylation under Friedel-Crafts conditions occurs in the 6-position (78CR(C)(287)333>. 

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