Thiophenes nucleophilic substitution

Phenanthro[l,2-d][l,2,3]selenadiazole, 10,11 dihydro- H NMR, 6, 348 synthesis, 6, 353 Phenanthro[b]thiophenes synthesis, 4, 914 Phenanthro[4,5-bcd]thiophenes synthesis, 4, 883, 907, 914 Phenanthro[9,10-ej[l, 2,4]triazines synthesis, 3, 434 Phenarsazin synthesis, 1, 561 Phenazine dyes, 3, 196-197 nitration, 3, 177 UV Spectra, 2, 127 Phenazine, 3-amino-2-hydroxy-in colour photography, 1, 374 Phenazine, 1-chloro-nucleophilic substitution, 3, 164-165 5-oxide... 

The halogens of halothiophenes are more labile than those of the corresponding benzenes in accordance with theoretical considera-tions which indicate that thiophenes should also undergo nucleophilic substitutions more rapidly than benzenes. Hurd and Kreuz" found that in qualitative experiments 3,5-dinitro-2-chlorothiophene was more reactive toward piperidine and methanolic potassium hydroxide than 2,4-dinitrochlorobenzene. A quantitative study on the reaction of the six isomeric bromonitrothiophenes with piperidine (Table V) shows that the thiophenes react about one thousand times... 

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-... 

Metalation of Thiophenes with Organolithium Compounds (Nucleophilic Substitution on Hydrogen)... 

Millan and coworkers (99-101) also studied the effect of tacticity on the nucleophilic substitution reactions of PVC. Sodium thiophenate and phenol were used for these reactions. The central chlorine in isotactic triads and, to a lesser extent, in heterotactic triads was found to be most reactive. It was concluded that initiation of degradation may occur by normal structures, and polyene build-up may be favored by syndiotic sequence. This... 

Such configurational as well as conformational effects have been also reported by MILLAN et al. in the case of nucleophilic substitution of poly(vinyl chloride) with sodium thiophenate (14) and with sodium isooctylthioglycolate or isooctylthiosalicylate (15). The authors have shown that these reactions proceed selectively on the isotactic TT diads which can only exist either in the GTTG isotactic or in the TTTG heterotactic triads, the former ones being much more reactive than the latter ones. 

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. 

Such nucleophilic displacements are likely to be addition-elimination reactions, whether or not radical anions are also interposed as intermediates. The addition of methoxide ion to 2-nitrofuran in methanol or dimethyl sulfoxide affords a deep red salt of the anion 69 PMR shows the 5-proton has the greatest upfield shift, the 3- and 4-protons remaining vinylic in type.18 7 The similar additions in the thiophene series are less complete, presumably because oxygen is relatively electronegative and the furan aromaticity relatively low. Additional electronegative substituents increase the rate of addition and a second nitro group makes it necessary to use stopped flow techniques of rate measurement.141 In contrast, one acyl group (benzoyl or carboxy) does not stabilize an addition product and seldom promotes nucleophilic substitution by weaker nucleophiles such as ammonia. Whereas... 

Nucleophilic substitution of thiophene can also be enabled by the presence of electron withdrawing groups (e.g., -CHO <00SC1359>, -COMe <00T7573>, -NO2 <00JCS(P1)1811>) on carbon. The regioselectivity of the addition of amine nucleophiles onto 3,5-dibromothiophene-2-carboxaldehyde (54) has been studied and found to be independent of reaction conditions (para product 55 favored over ortho product 56) <00SL459>. 

This order of reactivity was observ for add dedeuteration, but for acetylation, formylation, and chlorination it was slightly different thieno[3,2-h]thiophene (2) > thieno[2,3-h]thiophene (1) > thiophene thieno[3,4-6]thiophene (3) was not studied. A substantially greater discrepancy between theoretical and experimental data was observed for nucleophilic substitution from the data on base dedeuteration and competitive metalation reactions/ the order of decreasing reactivity was as follows thieno[2,3-h]thiophene (1) > thieno[3,2-h]thiophene (2) > thiophene. To a certain extent this may be explained by differences in the mechanism of metalation and deuterium exchange with a base. A discrepancy between calculation and experiment was also found for free-radical substitution. ... 

Nucleophilic substitution procedures are also of use of the synthesis of j3-chlorinated thiophenes. Copper(I) chloride converted 3-bromothio-phene into its chloro analogue. Such reactions are best carried out in an... 

Studies on the Chemistry of Thienoannulated 0,N- and S,N-Containing Heterocycles. 1. Nucleophilic Substitution Reactions on Chlorinated Thiophene Derivatives as a Basis for the Synthesis of Thienoannulated 0,N- and S,N-Heterocycles, Puschmann, I. Erker, T. Heterocycles 1993,36,1323. See also Studies on the Chemistry of Thienoanellated 0,N- and S,N-Containing Heterocycles. II. Synthesis on Thieno-Dilthiazem Analogs, Puschmann, 1. Erker, T. Heterocycles 1995, 41, 709. 

In the thiophene (75JHC327) and benzothiophene (78JOC4379) series, nucleophilic substitution of hydride ion (Scheme 31) becomes possible due to the ability of 3d-orbitals of the sulfur atom to stabilize negative charge arising in the anionic cr-complex. 

Nucleophilic substitution of (189b) with methoxide ion gave the methoxy substituted compound, which, however, reacted further to give deboronated thiophenes. Copper-promoted nucleophilic substitution of some 4-brominated thieno fused diazaborines can be carried out successfully (equations 13 and 14) <77CS<11)76). 

If the thiophene ring bears one or more N02 groups, it becomes susceptible to nucleophilic attack by alkoxide ion an anionic cr-complex is thus produced which can be isolated in some cases. This is called a Meisenheimer adduct, and corresponds to the first step in many nucleophilic substitution reactions on activated thiophene substrates. The similarity between these adducts and heterocyclic pseudobases has been pointed out (79AHC(25)l). Kinetic data lead to similar rate equations for both processes both are characterized by negative entropies of activation of similar magnitude. 

Numerous syntheses involving formation of the thiophene ring have been reported. Nucleophilic substitution by ethyl mercaptoacetate of 2-chloro-3-cyanopyridine with subsequent base-promoted cyclization yields ethyl 3-aminothieno[2,3-i]pyridine-2-carboxylic acid, which is easily transformed by standard methods into the parent compound (258 Scheme 63) (74JHC975, 76JHC273). 

Method B. The reactions starting from 2-chloro-3-cyanopyridines 12 and thiogly-colic acid derivatives involve nucleophilic substitution followed by thiophene ring closure in the presence of a basic catalyst. 

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