Selenophenes nucleophilic

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). 

Nucleophilic substitution reactions in the selenophene series have attracted some interest. Debromination of bromonitro compounds [(50, X = S, Se) and (53, X = S, Se)] with sodium thiophenoxide and sodium selenophen-oxide72 was studied. Selenophene compounds were four times more reactive than the thiophene derivatives. The position of attack, a or /), had very little influence on the rate ratio. The kinetics of the side-chain nucleophilic reactions of selenophene derivatives, shown in Scheme 4, has been reported.7 3... 

Selenophene compounds react faster than the corresponding thiophene derivatives in both electrophilic and nucleophilic substitutions. This may be due to the capacity of selenophene to delocalize both positive and negative charges, since the selenium atom is larger and more polarizable than the sulfur atom and consequently selenophene can release its p-electrons and accept electrons into its free -orbitals more readily than thiophene. 

A way to introduce the primary amino group directly onto the selenophene ring is via the azido compound, obtained by nucleophilic substitution of the bromo derivative with sodium azide. Useful transformations of the azido group are shown in Scheme 12.117 The amino aldehyde (109) is a suitable starting material for the preparation of selenolo[3,2-b]pyridine (110) by the Friedlander reaction.138 Not only can the azido be reduced to an amino... 

Experimental precautions are required for NMR measurements in this group because the adducts rapidly undergo ring opening. The NMR spectra of the selenophene adducts in solution are similar to those of the corresponding thiophene adducts. The H-NMR data for adducts 142-145, as obtained from dinitro and cyanonitroselenophene derivatives, are reported in Table XXI. It is of interest that, unlike 2-cyano-4-nitrothiophene, its selenophene analog is converted to the anionic a-adduct by nucleophilic attachment at the unsubstituted C-5 position without any competition from a reaction at the CN side chain.169... 

Five-membered heterocycles also capable to ring-opening and recyclisation processes by nucleophile action. Well known examples include the interconversions of pyrrole, furan, thiophene and selenophene rings e.g. furan and ammonia over a suitable catalyst can give pyrrole (82KGS418), (80DOK1144). 

Lithiated selenophenes and tellurophenes have been used as intermediates in the preparation of a wide range of derivatives. A comprehensive tabulation of these transformations is available (790R(26)l) and this illustrates the large number of electrophiles which have been reacted with selenienyl- and, to a lesser extent, tellurienyl-lithiums. An extension of the synthetic potential of these lithiated derivatives is achieved by first converting them into iodonium salts (111), which may then be reacted with nucleophiles (Scheme 12) (74SC63). 

Selenophene does not react with nucleophilic reagents by substitution or addition but only by proton transfer. Other selenaheterocycles such as 1,2- and 1,3-selenazoles, selenadiazoles, and particularly seleninium salts are susceptible to nucleophilic attack at the carbon atoms of selenaaromatic rings. 

The reactivity sequence furan > selenophene > thiophene > benzene has also been observed in the nucleophilic substitutions of the halogenonitro derivatives of these rings.21,22 This shows that the observed trend does not depend on the effectiveness of lone-pair conjugation of the heteroatoms NH, O, Se, and S and the 77-electron density at the carbon atoms. It is interesting to note that a good correlation is observed between molecular ionization potentials (determined from electron impact measurements) and reactivity data in electrophilic substitution, in that higher reactivities correspond to lower ionization potentials182 pyrrole furan < selenophene < thiophene benzene (see Table VII). This is expected in view of a... 

BTMSBD reacts with a variety of nucleophiles to give novel heterocycles such as selenophen tellurophen and pyrazoles. It has also been used 1n [2+4] cycloaddition/cycloreversion sequences to prepare ethynyl-substituted Pyridazlnes and furans. ... 

Selenophene compounds are also more reactive in nucleophilic substitutions. Thus, 3-nitro- and 5-nitro-2-bromoselenophenes90 react with piperidine faster than do the corresponding thiophenes.91 The effect of electron-accepting substituents on the nucleophilic substitution of bromine located at the 2-position of 3,5-disubstituted selenophenes has been studied, as also has the applicability of the Hammett equation to this piperidino-debromination.92... 

Thus, the kinetic results show that selenophene undergoes both electrophilic and nucleophilic substitution reactions somewhat more readily than does thiophene. Hence, the reactivity of the heterocycle increases when sulfur is replaced by selenium a possible explanation might be that the selenium atom is larger and more polarizable, and therefore more willing both to release its p electrons and to accept electrons into its free d orbitals. 

Palladium chemistry is useful for linking selenophene and an activated carbon nucleophile (Equation 5). Treatment of 2-iodoselenophene with sodium malonitrile in the presence of a palladium(ll) catalyst provided malonitrile derivative 46b formed by tautomerization of the initial adduct 46a <1996H(43)1927>. 

A new solvent was investigated for the introduction of amine nucleophiles onto the selenophene nucleus via nucleophilic aromatic substitution. Treatment of 5-bromoselenophene-2-carboxaldehyde 53 with secondary amines in water produced 5-aminoselenophenes 54 (Equation 6) <1999T6511>. 

The addition of an alkyllithium nucleophile onto a 2-acylselenophene was the key step in the preparation of a selenophene-based tamoxifen derivative 68 <1997JCM274>. 

Nucleophilic substitution of halogen in 2-(3)halo-3-(2)formylbenzo[ft]selenophenes by nitrogen-containing nucleophiles is the first step for the formation of new tricyclic compounds <83JHC49>. 

The role of Meisenheimer complexes was studied in the nucleophilic substitution of the nitro group by methoxide anion in 2- and 3-trifluoromethylsulfonyl-4- and 5-nitroselenophenes <83JCR(S)58>. The use of potassium thiocyanate and selenocyanate as nucleophiles with 3-bromo-2-nitro-selenophene has allowed the elaboration of several condensed bicyclic selenophenes <83JHC113> as shown in Structures (10) and (11). 

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