Thiophene and Selenophene

This reaction generates a carbanion in a o orbital in the rate-determining step (Chapter 2, Section 2.A) and so does not directly involve the ir cloud. Inductive effects are therefore of primary, and conjugative effects only of secondary, importance. The 2- 3-position rate ratio for deuteria-tion of thiophene in DMSO at 25°C is 2.5 x 105 (64MI3, 64MI4 66MI2), but no direct comparison with benzene is available thiophene is likely to 

Relative Rates of Substitution of Thiophenes RC4H,S in Base-Catalyzed Deuteration 

As in thiophene, both 3- and 5-methyl groups in furan deactivate the exposition —10-fold (66CHE643). 

Three main conditions have been used for nitrating thiophenes. 

For thiophene itself, conditions of type (1) tend to produce very fast reactions. However, work has shown that the explosively fast reaction with nitric acid-acetic acid, due to nitrosation, can be largely suppressed by using urea [71 JCS(B) 102] and sulfanilic acid would probably be even better in this respect [cf. 77JCS(P2)248, 77JCS(P2)1693]. Conditions (1) have therefore been confined mainly to deactivated thiophenes, with conditions (2) being preferred for activated thiophenes. It is believed that acetic anhydride suppresses side reactions preceeding via nitrosation under conditions (2) [71 JCS(B) 102]. 

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Thiophene and selenophene can be chloromethylated by treatment with formaldehyde and hydrochloric acid. Depending on the conditions, 2-chloromethyl or 2,5-bis(chloromethyl) derivatives are obtained. The chloromethylation of benzo[6]thiophene gives the 3-chloromethyl derivative and that of benzo[6]furan the 2-chloromethyl compound (71AHC(13)235). 

The carbonyl reactivity of pyrrole-, furan-, thiophene- and selenophene-2- and -3-carbaldehydes is very similar to that of benzaldehyde. A quantitative study of the reaction of iV-methylpyrrole-2-carbaldehyde, furan-2-carbaldehyde and thiophene-2-carbaldehyde with hydroxide ions showed that the difference in reactivity between furan- and thiophene-2-carbaldehydes was small but that both of these aldehydes were considerably more reactive... 

Rates of debromination of bromonitro-thiophenes and -selenophenes with sodium thio-phenoxide and sodium selenophenoxide have been studied. Selenophene compounds were about four times more reactive than the corresponding thiophene derivatives. The rate ratio was not significantly different whether attack was occurring at the a- or /3-position. As in benzenoid chemistry, numerous nucleophilic displacement reactions are found to be copper catalyzed. Illustrative of these reactions is the displacement of bromide from 3-bromothiophene-2-carboxylic acid and 3-bromothiophene-4-carboxylic acid by active methylene compounds (e.g. AcCH2C02Et) in the presence of copper and sodium ethoxide (Scheme 77) (75JCS(P1)1390). 

In the thiophene and selenophene series, a-halogens are preferentially removed by reduction with zinc and acetic acid, as is illustrated by the preparation of 3-bromothiophene... 

Addition reactions with tetracyanoethane have provided access to 2,5-diamino-3,4-dicyano-thiophene and -selenophene (58JA2775,81ZOR1958). Base catalyzed rearrangement gives the isomeric pyrrolethiol (Scheme 53). 

Although no experimental details were given, it was stated that the relative reactivities of the 2 positions of furan, thiophene and selenophene were 1 500 ... 

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>. 

The electronic structures of furan, thiophene, and selenophene, their protonated complexes, and their anions have been calculated by the extended Hiickel method.6 The results of these calculations have been used to determine the influence of the heteroatom on the degree of aromaticity and electron density. 

The main dilference between thiophene and selenophene is that on flash photolysis in the former SH and not S2, while in the later Se2 and not SeH were detected in the photodecomposition products. This suggests that in selenophene the dissociation takes place at the Se site and that Se2 is formed as a result of the recombination of the Se atoms.24... 

Recently, the hydroxy derivatives of furan, thiophene, and selenophene have been studied with regard to their physical properties and reactions. These compounds are tautomeric and if the oxygen function is placed in the 2-position they exist as unsaturated lactones and undergo carbon-carbon rearrangement, whereas the 3-hydroxy derivatives form oxo-enol tautomeric systems. By NMR the structures of the different tautomeric forms have been determined as well as the position of the tautomeric equilibrium and the rate of isomerization. 

Acyl azides 268, derived from furan, thiophene and selenophene, add slowly at room temperature to the strained double bond of 5-methylenebicyclo[2.2.1]hept-2-ene. Two regioisomeric triazolines, 269 and 270, which form in the first step, are unstable and decompose with elimination of nitrogen to provide aziridine derivatives 271. Products 271 are isolated in good yield (73-85%). It is worthy to note that not only the terminal, unstrained double bond in the starting material, 5-methylenebicyclo[2.2.1]hept-2-ene, is unaffected, but also the typical dipolarophiles like esters of crotonic, propiolic and byt-2-ynoic acids do not react with azides 268 under these conditions (Scheme 39) <2002J(P1)1420>. 

These effects can occur when the active site at which a measurable phenomenon occurs is in close proximity to the substituent. Among the many systems exhibiting direct steric effects are ortho-substituted benzenes, 1, cis-substituted ethylenes, 2, and the ortho- (1,2-, 2,1- and 2,3-) and peri- (1,8-) substituted naphthalenes, 3, 4, 5 and 6, respectively. Other examples are d.v-1,2-disubstiUited cyclopropanes, c/ s-2,3-disubstituted norbornanes and ci.s-2,3-disubstituted [2.2.2]-bicyclooctanes, 7, 8 and 9, respectively. Some systems generally do not show steric effects. Vicinally substituted systems such as disubstituted methanes, 10, and 1,1-disubstituted ethenes, 11, are examples, 2,3-Disubstituted heteroarenes with five-membered rings such as thiophenes and selenophenes... 

Furans, thiophenes and selenophenes react similarly, but with the reactivity decreasing from tellurophens to furans. 

The PMR spectra of thiophene and selenophene have been thoroughly studied. The close similarity of the spin-sirin coupling... 

Substituting a formyl, carboxy, or carbalkoxy group into a thieno-thiophene or selenophenothiophene molecule has no substantial effect on Ae coupling constants but considerably affects the chemical shifts (see Litvinov and Fraenkel and Michael and Gronowitz ). The chemical shifts of the protons in the selenophene ring are characteristic of different t rpes of condensation of the thiophene and selenophene rings and increase in the order 15 > 14 > 16 irrespective of the solvent used (acetone, CCIJ. A similar sequence is observed in the carbonyl derivatives of the isomeric selenophenothiophenes. 

C. Paulmier, J. Morel, D. Bernard, and P. Pastour, Synthesis and chemical properties of carbonylated and hydroxylated thiophenes and selenophenes. Bull. Soc. Chim. Fr., 2434 (1973). 

Substituents at C(4) do not appreciably modify the conformational equilibrium of the 2-formyl group in furan, pyrrole, thiophene, and selenophene derivatives (81RCR336). 

Furans, Thiophenes and Selenophenes with Fused Six-membered Heterocyclic Rings... 

Rate and Equilibrium Constants for the Formation of u-Adducts by the Reaction of Some Thiophene and Selenophene Derivatives with MeO" in MeOH, at 25°C... 

The comparison between thiophene and selenophene compounds has received close attention in detailed quantitative work by Terrier et a/.36,174 As shown in Table XXV, when the reagent attacks a CH position, the equilibrium constants for the formation of the selenophene adducts 142, 144, and 145 are about two orders of magnitude greater than those of the... 

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